Showing papers in "Acta Neuropathologica in 1990"
TL;DR: Neurons of Area 11 in the fronto-orbital cortex of 18 unselected AIDS brains are analyzed by means of stereology and damage to the cerebral cortex in AIDS is confirmed, which has been described only qualitatively as diffuse poliodystrophy.
Abstract: Neurons of Area 11 in the fronto-orbital cortex of 18 unselected AIDS brains are analyzed by means of stereology. Neurological abnormalities including dementing symptoms were described in eight patients. Neuropathology diagnosed human immunodeficiency virus (HIV)-specific changes in four, and diffuse poliodystrophy in eight brains. The majority (71.4%) of these brains was immunoreactive for HIV antigens when tested by immunocytochemistry. A significant loss of neurons is found as compared to normal controls. Neuronal density in AIDS brains is reduced by 18%, and the perikaryon volume fractions is reduced by 31%. Although only speculation on pathogenesis of this neuronal loss is possible at present, it may represent a part of the pathomorphological substrate of AIDS-related dementia. Moreover, it confirms by quantitative means damage to the cerebral cortex in AIDS which has been described only qualitatively as diffuse poliodystrophy.
344 citations
TL;DR: Findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinson's disease.
Abstract: We performed immunohistochemical analysis of specimens from three autopsied patients with Parkinson's disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinson's disease.
279 citations
TL;DR: A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus, and theFerritin/microglia system might be secondarily involved in the removal and processing of the amyloid.
Abstract: A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.
245 citations
TL;DR: The significance of the distribution of HIV-1-infected cells, especially microglia, with respect to cellular tropism and involvement of deep gray matter nuclei in a pattern reminiscent of a multisystem atrophy is discussed.
Abstract: Among 100 brains from patients with acquired immunodeficiency syndrome (AIDS), 33 brains (21 adults and 12 children) with histological evidence of subacute AIDS encephalitis were immunostained with one of the most sensitive antibodies to HIV-1 antigen, anti-gp41. Twenty-six (20/21 adults, 6/12 children) of the 33 brains showed pg41 positivity. Brains from children had fewer gp41-positive cells than brains from adults. The distribution of gp41-positive cells was characteristic. They were frequently detected and most numerous in the globus pallidus (medial > lateral). Although gp41-positive cells were prevalent, fewer were detected in the corpus striatum and thalamus. Of infratentorial areas involved, the ventral midbrain, especially the substantia nigra, and the dentate nucleus contained many positive cells. Lower levels of infections, often patchy, were noted in the cerebral and cerebellar white matter and pontine base. Gp41-positive cells were rarely seen in the cerebral cortex, medulla, spinal cord, leptomeninges, choroid plexus, ependyma, subependymal areas and endothelia. Besides immunoreactive macrophages and multinucleated cells, gp41-positive microglia with various morphological alterations were abundant in the deep cerebral gray matter, ventral midbrain and dentate nucleus. Most of these microglia were undetectable with conventional histological methods. We discuss the significance of the distribution of HIV-1-infected cells, especially microglia, with respect to cellular tropism and involvement of deep gray matter nuclei in a pattern reminiscent of a multisystem atrophy.
202 citations
TL;DR: The majority of patients with temporal lobe epilepsy show hippocampal sclerosis, which pathologically represents neuronal loss and gliosis, and the difference in neuronal density between the non-tumor epilepsy (NTE) and tumor-associated epilepsy (TAE) groups is discussed.
Abstract: The majority of patients with temporal lobe epilepsy show hippocampal sclerosis, which pathologically represents neuronal loss and gliosis. We studied volumetric neuronal density on a representative mid to mid-posterior level slice of hippocampi surgically removed from intractable temporal lobe epilepsy cases, and compared the results between 25 non-tumor epilepsy (NTE) cases and 5 tumor-associated epilepsy (TAE) cases. Eleven age-matched non-epileptic autopsy cases were studied as controls. Cells were counted in the CA1 through CA4 fields and the stratum granulosum of the dentate fascia. In NTE every hippocampal field showed statistically significant loss of neurons, the neuronal density in each field ranging from 35% to 50% of that of control. The mean neuronal density between the TAE and NTE groups also showed statistically significant differences in all hippocampal fields. The neuronal density of hippocampal fields of NTE ranged from 43% to 58% of that of TAE. Tumor-associated epilepsy cases, however, failed to show any statistically significant deviation from the control in their neuronal density. The etiology of the difference in neuronal density between the TAE and NTE groups is discussed.
199 citations
TL;DR: The central neurocytoma can be reliably diagnosed using antibodies to neuron-specific enolase and synaptophysin, and that histogenetically, this neoplasm is derived from a neuroectodermal precursor cell capable of both, neuronal and glial differentiation.
Abstract: Central neurocytoma has been characterised by its intraventricular localisation, predominant occurrence in young adults, oligodendroglioma-like histology, benign course and ultrastructural evidence for neuronal differentiation. Eleven intraventricular central neurocytomas were studied histopathologically, employing cell type-specific immunocytochemical markers and electron microscopic analysis. In the past, these lesions have caused diagnostic problems since central neurocytomas share basic histopathological features with other periventricular neoplasms. Accordingly, several tumours of this series had previously been classified as ependymomas of the foramen of Monro or oligodendrogliomas. Although generally regarded as benign lesions, two central neurocytomas of this series showed histopathological evidence of anaplasia, with focal necrosis, mitotic activity and vascular proliferation. All central neurocytomas exhibited immunoreactivity for neuronspecific enolase and synaptophysin, indicating consistent neuronal differentiation. Three tumours were studied by electron microscopy and contained synaptic vesicles, neuritic processes and neurosecretory granules. In addition, one tumour contained ganglioid cells and this was associated with focal immunoreactivity for neurofilament protein, suggesting that some central neurocytomas may, at least focally, continue to differentiate towards the formation of mature neurons. Two of the tumours expressed glial fibrillary acidic protein in a considerable percentage of neoplastic cells which demonstrates a capacity for bipotential, i.e. glial and neuronal differentiation. We conclude that the central neurocytoma can be reliably diagnosed using antibodies to neuron-specific enolase and synaptophysin, and that histogenetically, this neoplasm is derived from a neuroectodermal precursor cell capable of both, neuronal and glial differentiation. The hypothesis is proposed that the central neurocytoma originates from the subependymal plate of the lateral ventricles, an embryonal matrix cell layer which postnatally maintains a limited proliferative potential.
193 citations
TL;DR: In Down's syndrome (either associated or not to AD) thin basilar dendrites were the most severely involved; in AD patients CA1 pyramids were more severely affected than pyramidal neurons of the CA2–3 subfield.
Abstract: Samples of the hippocampus of four patients with Down's syndrome [two men aged 35 and 36 years with no evidence of Alzheimer's disease (AD) and two patients aged 47 and 55 years with associated AD] were obtained at post mortem and processed according to the rapid Golgi method. A significant reduction in the number of dendritic spines (DS) was found in the apical (middle, distal and oblique segments) and basilar (thick and thin segments) dendritic arbors of CA1 and CA2–3 pyramidal neurons in patients with Down's syndrome and no AD when compared to age-matched controls. An additional decrease of DS in every segment occurred in Down's patients with associated AD when compared to agematched controls and Down's patients with no AD. In Down's syndrome (either associated or not to AD) thin basilar dendrites were the most severely involved; in AD patients CA1 pyramids were more severely affected than pyramidal neurons of the CA2–3 subfield.
190 citations
TL;DR: Modifications in vascular density are present in AD brains with a marked regional specificity, and vessels in the AD brains exhibited extensive topographical changes, such as kinking and looping.
Abstract: It was the aim of this study to determine, qualitatively and quantitatively, alterations in the blood vessels of brains removed postmortem from patients with Alzheimer's disease (AD), and to compare these findings with the appearance of cerebral blood vessels in a group of individuals without brain disorders. Celloidin sections of brain tissue from four cerebral areas, pre-frontal (Brodmann's area 9), basal forebrain, sensorimotor, and hippocampus, were subjected to an alkaline phosphatase reaction to facilitate the evaluation of the vascular distribution. The vascular density in five sections was determined by counting the number of vascular intersections with a microscopic test grid of 100 squares; ten fields per section were examined in this manner. Analysis of 16 AD and 6 control brains, showed that there was a striking and statistically significant reduction in the vascular net density specifically in the basal forebrain region and the hippocampus of AD brains. In addition, vessels in the AD brains exhibited extensive topographical changes, such as kinking and looping. These results indicate that modifications in vascular density are present in AD brains with a marked regional specificity.
172 citations
TL;DR: Ultrastructural, three-dimensional reconstruction and morphometric studies of classical plaques from the cortex of a patient with Alzheimer's disease showed five or six microglial cells, which form the central complex of the classical plaque.
Abstract: Ultrastructural, three-dimensional reconstruction and morphometric studies of classical plaques from the cortex of a patient with Alzheimer's disease showed five or six microglial cells, which form, together with the amyloid star, the central complex of the classical plaque. Microglial cells associated with the amyloid star show marked polymorphism, but all forms possess an amyloid making pole. The surface of the cell membrane at this pole is extended by apparent connection with membranes of cytoplasmic channels filled with amyloid fibers. The amyloid pole also shows other features of local activation with nuclei translocation, expansion of Golgi apparatus and endoplasmic reticulum, and multiplication of vacuoles and coated vesicles that are in close proximity to channels filled with new polymerized amyloid fibers. On the basis of ultrastructural studies, three forms of microglial cells can be distinguished: macrophage-like, cap-like, and octopus-like cells. The most effective in production of amyloid fibers seem to be cap-like microglial cells, which have the greatest interface with the amyloid star. Octopus-like cells have the least contact with the amyloid star. The size of the surface of the interface with the amyloid star appears to be an indicator of the extent of cell engagement in amyloid fiber formation.
165 citations
TL;DR: Dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy and correlated well with clinical assessments of the disease severity expressed in patients.
Abstract: This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular, dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter-and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients: We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy.
141 citations
TL;DR: The data indicate that the process of amyloidosis in AD and in elderly DS patients is not restricted to the cerebral cortex and may affect other grey matter regions, particularly the cerebellum.
Abstract: The extent of amyloid deposition within the cerebellum and the cerebral cortex was assessed and compared, using anti-amyloid protein (A4) immunostaining and a novel methenamine silver method, in 20 patients aged between 60 and 77 years with Alzheimer's disease (AD), 29 patients aged between 13 and 71 years with Down's syndrome (DS), 26 demented patients with disorders other than AD and DS and in 20 non-demented elderly individuals of age range 60–102 years. In AD, amyloid deposits were noted in the cerebellar cortex in 90% of patients and in the meningeal vessels of the cerebellum in 80% of patients. In DS, amyloid deposits were seen in the cerebellar cortex in 82% of patients over 30 years of age and was universal in patients over 50 years of age. Overall, in DS, amyloid deposits were present in the meningeal vessels of the cerebellum in 79% of patients, but were present in 94% of those patients over 50 years of age. The sites of amyloid deposition in the cerebellar cortex were (poorly) detected by lectin histochemistry (Concanavalin A binding) in only 40% of patients with AD and 43% of all patients with DS (69% of those over 50 years of age). No amyloid deposits were seen in either the cerebellar cortex or its meningeal vessels in any of the 20 non-demented elderly individuals nor in any of the non-Alzheimer demented patients. The cerebellar amyloid deposits were never associated with a neuritic change [i.e. as characterised by the presence of (taupositive) paired helical filaments (PHF)] and neurofibrillary tangles were seen only in a few cells of the dentate nucleus in a single patient with AD and in three of the elderly DS patients. Amyloid deposits were numerous in the cerebral cortex of all patients with AD and in all, except the 13-year-old patient, with DS. In all the AD patients and in most of the DS patients over 30 years of age, many of the cerebral cortical amyloid deposits were associated with neurites and were strongly recognised by lectin histochemistry. Amyloid deposits were present within the meningeal vessels of the cerebral cortex in 75% patients with AD and 72% of patients, over 30 years of age, with DS (82% of those over 50 years of age). These data indicate that the process of amyloidosis in AD and in elderly DS patients is not restricted to the cerebral cortex and may affect other grey matter regions, particularly the cerebellum. However, it seems to be only in the cerebral cortex that such deposits are widely associated with a ‘reactive’ neuritic (PHF) change and an accumulation of saccharide. It is probably these latter alterations that mark the process of neuronal (neurofibrillary) degeneration that leads to functional deficits.
TL;DR: It was considered to be an important neuropathological finding that some of the remaining pontine neurons affected by OPCA developed characteristic cytoplasmic argyrophilic inclusions.
Abstract: Patients with olivopontocerebellar atrophy (OPCA) were studied, and cytoplasmic inclusions were observed in some of the remaining neurons of the pontine nuclei, nuclei reticularis tegmenti pontis and arcuate nuclei. The cytoplasmic argyrophilic inclusions were demonstrated by silver impregnation techniques such as Bielschowsky and Bodian staining. With hematoxylin and eosin stain, the inclusions were sharply demarcated and appeared pale. The inclusions were not stained by the following routine histological methods: Kluver-Barrera, phosphotungstic acid hematoxylin, Holzer, periodic acid-Schiff, Mallory azan, alcian blue, nile blue, Masson trichrome, Congo red, thioflavine S, oil red O and Sudan black B stains. Immunohistochemistry with anti-ubiquitin antiserum showed that these inclusions were ubiquitinated. However, the inclusions did not react with any of the following antibodies (Abs) or antisera: anti-phosphorylated neurofilament (NF) Ab, anti-nonphosphorylated NF Abs (160 and 200 kDa), anti-paired helical filament antiserum, anti-tau antiserum, anti-tubulin Abs (alpha and beta), anti-microtubule-associated proteins antiserum, anti-glial fibrillary acidic protein antiserum, anti-vimentin Ab, anti-desmin Ab, anti-cytokeratin Abs (low and high molecular weights), anti-actin antiserum, anti-skeletal myosin antiserum and anti-myelin basic protein Ab. Ultrastructurally, the inclusion bodies noted in OPCA were composed primarily of fibrils having a width ranging from about 24 to 40 nm, which were entirely coated with osmiophilic granular material along their whole length. They were occasionally intermingled with a few filaments about 10 nm in width. Electron microscopical examination on silver-impregnated specimens revealed that each granule-coated fibril had a great affinity for silver particles. In elucidating the pathogenesis of OPCA, it was considered to be an important neuropathological finding that some of the remaining pontine neurons affected by OPCA developed characteristic cytoplasmic argyrophilic inclusions.
TL;DR: A significant positive correlation was found between the number of RM3/1 or CR3 (CD11b)-positive cells and the proliferation rate of the tumors as documented by thenumber of bromodeoxyuridine-positive or Ki-67+ cells.
Abstract: Cryostat sections of 12 gliomas and of 3 peritumoral brain tissue samples were investigated for mononuclear cell infiltration by immunohistochemistry, concentrating on cells expressing monocyte/macrophage markers. Only low numbers of T cells were detected in the tumors, whereas in average 20%–30% of all cells present in the samples were recognized by various macrophage markers. These cells carried surface epitopes with known function, like Fc-γ (Fcg) and complement receptors. Microglial cells, in comparison to typical debris laden macrophages, were only recognized by a restricted panel of macrophages markers (anti-Fcg receptors 1, 2, 3, complement receptor CR3, HLA DR, common leucocyte antigen CD45 and the monocyte marker RM3/1). In peritumoral tissue mainly dendritic, microglia-like cells were present, which revealed decreased expression of antigens CD4, RM3/1 and Fcg receptors in comparison to those in gliomas. A significant positive correlation was found between the number of RM3/1 or CR3 (CD11b)-positive cells and the proliferation rate of the tumors as documented by the number of bromodeoxyuridine-positive or Ki-67+ cells.
TL;DR: The applicability of the method to experimental neuropathology is demonstrated by Golgi-like staining of “dark” neurons in rat brains exposed to various pathological conditions including ischemia, hypoglycemia, trauma, status epilepticus, deafferentation and poisoning with kainic acid, colchicine and sodium azide, respectively.
Abstract: A silver method is proposed for the selective, well-contrasted and reproducible demonstration of "dark" neurons in frozen, vibratome and paraffin sections cut at a thickness of 5 to 200 microns from aldehyde-fixed brains. The Golgi-like staining of the dendrites enables assorting of "dark" neurons according to characteristic neuron classifications. The staining procedure includes an esterification with 1-propanol, a treatment with diluted acetic acid and development. The esterification strongly increases the argyrophilia of both "dark" neurons and mitochondria. Unwanted co-staining of mitochondria is suppressed by the acetic acid treatment, while a special developer is used to render the staining controllable. The applicability of the method to experimental neuropathology is demonstrated by Golgi-like staining of "dark" neurons in rat brains exposed, before transcardial perfusion-fixation and delayed autopsy, to various pathological conditions including ischemia, hypoglycemia, trauma, status epilepticus, deafferentation and poisoning with kainic acid, colchicine and sodium azide, respectively.
TL;DR: Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on invasion of nerves by non-resident macrophages and the role of the macrophage complement receptor type 3 (CR3) in myelin removal is clarified.
Abstract: Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on invasion of nerves by non-resident macrophages. The present study was done to clarify the role of the macrophage complement receptor type 3 (CR3) in myelin removal. Myelin phagocytic capacity of invading macrophages was abolished by treatment of cultured nerves and macrophages with anti-CR3 antibody or by serum complement depletion with cobra venom factor. This indicates that myelin phagocytosis is mediated by the macrophage CR3.
TL;DR: The results show that p-CPA can markedly modify the edema and the cellular changes occurring in the traumatic spinal injury and indicate that serotonin is somehow involved in the production of the early, and thus important, pathological events.
Abstract: The possibility that serotonin can modify the early pathological sequences occurring in spinal cord trauma was investigated in a rat model. To that end we took advantage of the possibility of influencing serotonin pharmacologically by treating animals with a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before the production of the injury and compared the results with injured, untreated controls. A unilateral incision was made into the dorsal horn of the lower thoracic cord (about 2.5 mm deep, 4.5 mm long) and the trauma. The injured region from untreated animals showed macroscopically at that time a pronounced swelling and the water content had increased by 3.5% as compared to intact controls. The segments rostral and caudal to the lesion also exhibited a profound increase in water content. Light microscopy revealed a significant expansion of the spinal cord as compared to controls. The swelling was most pronounced in the gray matter on the injured side. Electron microscopy showed distorted neurons, swollen astrocytes and extracellular edema in the gray matter in and around the primary lesion. There was also a sponginess in the surrounding white matter with disruption of myelin, collapsed axons and widened periaxonal spaces. Pretreatment of the rats with p-CPA significantly reduced the swelling of the injured spinal cord and there was no visible expansion. The ipsilateral edema in the central gray matter was considerable less pronounced as compared to that in untreated animals. The increase in water content was less than 1% in these animals. The neuronal and glial cell changes were also markedly reduced in the drugtreated rats. The disruption of myelin and the vacuolation of the gray matter were much less severe. Our results show that p-CPA can markedly modify the edema and the cellular changes occurring in the traumatic spinal injury and indicate that serotonin is somehow involved in the production of the early, and thus important, pathological events.
TL;DR: Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis, Werdnig-Hoffmann's disease, X-linked recessive bulbospinal neuronopathy and multiple system atrophy were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments.
Abstract: Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.
TL;DR: It is demonstrated that Tau proteins are normal and major components of the somatodendritic domain and that Tau pathology, reflected by the presence of Tau 64 and 69, affects preferentially this domain during Alzheimer's disease.
Abstract: Bundles of paired helical filaments (PHF) accumulate in the pyramidal neurons that degenerate during Alzheimer's disease. This neurofibrillary degeneration is highly correlated with clinical signs of dementia. During the degenerating process, Tau proteins, which are the major antigenic components of PHF, are abnormally phosphorylated and two pathological isoforms named Tau 64 and 69 are expressed. We have studied their immunoblot distribution in the cortical gray and white matter from different regions of normal and Alzheimer brains, to determine if the degenerating process preferentially affects the somatodendritic or the axonal domain. Two categories of antibodies were used. The first category consisted of anti-human native Tau, anti-Tau proteins from different vertebrates, anti-PHF, monoclonal antibody Alz-50 and an anti-C terminal repeated region of Tau. In control brains, these antibodies strongly detected normal Tau proteins in the gray matter while Tau immunodetection was weak in the white matter. In Alzheimer brain cortices, each antibody detected Tau 64 and 69 in gray matter extracts but not at all in white matter extracts. The second category of anti-Tau consisted of the anti-PHF saturated with normal brain protein extracts. This antiserum only probed the abnormally phosphorylated Tau proteins. It detected Tau 64 and 69 exclusively in the cortical gray matter of Alzheimer brains. Moreover, a 55-kDa Tau protein was also immunolabelled, which might be an intermediary form between normal Tau and Tau 64 and 69. Our results demonstrate that Tau proteins are normal and major components of the somatodendritic domain and that Tau pathology, reflected by the presence of Tau 64 and 69, affects preferentially this domain during Alzheimer's disease.
TL;DR: The proposed modifications of the WHO classification of meningiomas represent a compromise between the pathologist's need for a complete morphologic exposition and the clinician's desire for a concise classification of therapeutic and prognostic significance.
Abstract: The present WHO classification of meningiomas has served us well. In keeping with the adage, “if it ain't broke, don't fix it,” alterations should be made with due caution. These proposed modifications of the WHO classification are prompted by advances in our understanding of the pathobiology of meningeal neoplasms, as well as a need for an orderly scheme based upon factors of clinical importance. The author is well aware, that given the vastly differing technologies available to those utilizing the “blue book,” its application must have a basis in routine histology rather than in “high-tech” procedures. No classification is ideal, but the modifications suggested represent a compromise between the pathologist's need for a complete morphologic exposition and the clinician's desire for a concise classification of therapeutic and prognostic significance.
TL;DR: The present results clearly indicate that MAO-B activity is expressed in fibrillary astrocytes in or around senile plaques, suggesting that these astroCytes metabolize exogenous amines in senile Plaques.
Abstract: Monoamine oxidase (MAO) histochemistry has been performed in brains from patients with dementia of Alzheimer type (DAT) and aged controls. Conspicuous MAO-positive cell clusters were frequently observed in the amygdala, hippocampus, and insular cortex in the brains of DAT. Double staining with glial fibrillary acidic protein immunohistochemistry revealed that the clusterforming MAO-positive cells were astrocytes. Using Bielschowsky's method, Congo red and thioflavin S counterstaining, this astrocytic mass was shown to be associated with senile plaques. By the enzyme inhibition experiment, MAO activity in senile plaques was revealed to be of type B. The present results clearly indicate that MAO-B activity is expressed in fibrillary astrocytes in or around senile plaques, suggesting that these astrocytes metabolize exogenous amines in senile plaques.
TL;DR: Cases of old-aged demented individuals exhibited abundant cortical amyloid deposits but only small numbers of neurofibrillary changes, which may represent a variant of Alzheimer's disease or an initial stage of this disorder.
Abstract: Cases of old-aged demented individuals exhibited abundant cortical amyloid deposits but only small numbers of neurofibrillary changes. Neuritic plaques were rare or absent. Neither Ammon's horn nor isocortex revealed sufficiently large numbers of tangles to permit the diagnosis of fully developed Alzheimer's disease. Dense accumulations of neurofibrillary tangles and neuropil threads occurred only in layer Pre-alpha (II) of the entorhinal region. This pattern of cortical destruction may represent a variant of Alzheimer's disease or an initial stage of this disorder.
TL;DR: Muscle biopsies were obtained from the anterior tibial muscle of 15 healthy, sedentary young and 13 healthy and physically active elderly volunteers and obvious changes included some myofilament loss, collections of lipofuscin which were also observed in satellite cells, proliferation of the SR-T systems and increased wrinkling of nuclear membranes and sarcolemma.
Abstract: Muscle biopsies were obtained from the anterior tibial muscle (TA) of 15 healthy, sedentary young (23-37 years) and 13 healthy and physically active elderly (66-77 years) volunteers. The mean frequency of type I fibres was lower in the young subjects compared with the elderly, but the mean type I fibre cross-sectional area was equal in the two groups. The type IIA fibres were, however, smaller in the elderly than in young subjects. Capillary density, capillary per fibre ratio, capillaries in contact with type I fibres (CC) and CC in relation to type I and type II fibre area did not differ in the two groups. The number of capillaries in contact with type IIA fibres was higher in the younger group. Only occasional and minor pathological changes were observed in the young subjects. In the elderly, such changes were much more common, including central nuclei, ring fibres, fibre splitting, scattered highly atrophic fibres, moth-eaten fibres and vacuoles. Ring fibres were most easily identified with anti-desmin labelling and highly atrophic fibres exhibited a rough network of labelling. Increased content of actin and spectrin was also observed at the periphery of ring fibres. In the elderly group, a qualitative ultrastructural analysis was also obtained and obvious changes included some myofilament loss, collections of lipofuscin which were also observed in satellite cells, proliferation of the SR-T systems and increased wrinkling of nuclear membranes and sarcolemma.
TL;DR: Although the pathological findings were comparable with corticonigral degeneration with neuronal achromasia, several clinical and pathological features characteristic for progressive supranuclear palsy, progressive subcortical gliosis, and Pick's disease in this and the nine previously reported cases hampered the unequivocal nosological placement.
Abstract: A man, aged 58 years, suffered from progressive dementia, parkinsonism, and gaze paralysis for 30 months. Autopsy revealed severe degeneration of the substantia nigra, numerous swollen chromatolytic neurons within the cerebral cortex, scattered basal neurofibrillary tangles, and gliosis of the cerebral white matter and basal ganglia. Unusual globular inclusions positive for tau protein were detected within neurons of the upper cortical layers. Although the pathological findings were comparable with corticonigral degeneration with neuronal achromasia, several clinical and pathological features characteristic for progressive supranuclear palsy, progressive subcortical gliosis, and Pick's disease in this and the nine previously reported cases hampered the unequivocal nosological placement.
TL;DR: The present study indicates that even non-lethal ischemia can produce a severe inhibition of protein synthesis in the selectively vulnerable regions during the early stage of recirculation.
Abstract: Regional cerebral protein synthesis following brief ischemia was investigated in the Mongolian gerbil, utilizing l-[methyl-14C]methionine autoradiography. Transient ischemia was induced for 1,2 or 3 min. At various recirculation periods up to 48 h, animals received a single dose of l-[methyl-14C]-methionine and then were terminated 35 min later. Sham-operated animals showed a normal pattern of amino acid incorporation into the proteins of the brain. Following 1-min ischemia, the pattern of protein synthesis was similar to that in the sham-operated gerbils. Ischemia for 2 min, however, caused marked inhibition of protein synthesis in the neocortex, striatum, hippocampal CA1 sector and the thalamus at 1 h of recirculation. Extensive recovery of protein synthesis was found in the neocortex, the striatum, the hippocampal CA1 sector and the thalamus at 5–24 h of recirculation, but, a slight inhibition was detectable in the hippocampal CA1 sector in one of six animals. This inhibition had fully recovered at 48 h of recirculation. Following 3-min ischemia, severe impairment of protein synthesis was found in the neocortex, striatum, the whole hippocampus and the thalamus. After 5–24 h of recirculation, the protein synthesis in these regions had gradually recovered, except that complete lack of amino acid incorporation was seen in the hippocampal CA1 subfield. This impairment of protein synthesis in the hippocampal CA1 sector was not recovered at 48h of recirculation. Morphological study indicated that 2-min ischemia did not produce any significant neuronal damage in the brain, whereas gerbils subjected to 3-min ischemia revealed a mild neuronal damage in the hippocampal CA1 sector. The present study indicates that even non-lethal ischemia can produce a severe inhibition of protein synthesis in the selectively vulnerable regions during the early stage of recirculation.
TL;DR: Results indicate that PrP mRNA is a normal component in a variety of non-neuronal tissues and may explain the origin of the amyloid plaques present in the subependymal region of scrapie-infected brain.
Abstract: PrP 27-30, a unique protease-resistant protein associated with scrapie infectivity, derives from the proteolytic cleavage of a larger precursor encoded by a host gene. To identify sites of PrP biosynthesis, in situ hybridization was done using cloned PrP cDNA as a probe. In rodent brain, PrP mRNA was expressed in neurons, ependymal cells, choroid plexus epithelium, astrocytes, pericytes, endothelial cells and meninges of both scrapie-infected and uninfected animals. PrP mRNA was also detected in vitro in isolated brain microglia cells. Pulmonary cells and heart muscle cells contained high levels of this mRNA. Hybridization was not detected in spleen, confirming earlier RNA blot experiments indicating extremely low levels of PrP mRNA in this tissue. Results indicate that PrP mRNA is a normal component in a variety of non-neuronal tissues and may explain the origin of the amyloid plaques present in the subependymal region of scrapie-infected brain.
TL;DR: This immunocytochemical study examines the brains of squirrel monkeys for the presence and distribution of β/A4 amyloid, a 4-kilodalton peptide to indicate that the squirrel monkey can serve as a model for investigations of cerebrovascular amyloidsosis.
Abstract: In this immunocytochemical study, the brains of nine squirrel monkeys (Saimiri sciureus), ranging from 8 to 27 years of age, were examined for the presence and distribution of β/A4 amyloid, a 4-kilodalton peptide. In aged squirrel monkeys, amyloid is associated primarily with intracerebral and meningeal capillaries and arterioles and occurs to a lesser degree as small and/or diffuse deposits in the neural parenchyma and in the dense cores of senile plaques. Cerebrovascular amyloid is found primarily in neocortex, amygdala, and septum verum and is rare or nonexistent in other subcortical gray structures, white matter, cerebellum, and spinal cord; this pattern of localization is comparable to that in humans with cerebral amyloid angiopathy. There is a significant correlation between cerebrovascular and parenchymal deposits of amyloid. However, cerebrovascular amyloid is always the most abundant form in squirrel monkeys, even in cases of severe cerebral amyloidosis. In contrast to squirrel monkeys, aged rhesus monkeys (Macaca mulatta) develop, mostly parenchymal deposits of amyloid and have relatively less vascular amyloid. This species difference in the histological distribution of amyloid suggests that separate mechanisms may influence the accumulation of amyloid in cerebral blood vessels and in the neural parenchyma. These data also indicate that the squirrel monkey can serve as a model for investigations of cerebrovascular amyloidosis.
TL;DR: It is suggested that high AChE activity is intimately associated with the process of A4 protein formation and accumulation in plaques and that this association already occurs at a very carly stage of plaque formation.
Abstract: In 20 unselected autopsy cases tissue blocks from the hippocampus with adjacent entorhinal cortex and neocortex were stained for acetylcholinesterase (AChE). From five brains shown to have large numbers of senile plaques tissue, adjacent to that taken for AChE tissue blocks, was embedded in paraffin and sections were immunostained for the A4 protein. The morphological aspects were compared. Equivalent types of plaques and plaque-like structures were observed in the A4- and ACHE-stained sections. On selected tissue blocks from patients with many senile plaques two immediately adjacent cryostat sections were stained, one for AChE and one for A4 protein. The same individual plaques could be identified on the two sections. These findings suggest that high AChE activity is intimately associated with the process of A4 protein formation and accumulation in plaques and that this association already occurs at a very carly stage of plaque formation.
TL;DR: The possibility that microglia may play a fundamental role in the pathogenesis of amyloid deposition in the cerebellum in Alzheimer's disease is raised.
Abstract: Cerebellar amyloid deposits in Alzheimer's disease were studied by immunocytochemistry and with a series of antibodies that recognize human microglia, including anti-HLA-DR, LN-1, Leu-M5 and leukocyte common antigen. Microglia formed a dense reticular array throughout the cerebellum in areas with and without amyloid deposits. In areas with compact and reticular amyloid deposits, microglia had morphological features consistent with activation, such as cytoplasmic swelling and shortening and thickening of cell processes. In areas with diffuse amyloid deposits, microglia had delicate and highly ramified processes. Nevertheless, microglial cells or their processes were detected in association with amyloid deposits of all morphological types. These results raise the possibility that microglia may play a fundamental role in the pathogenesis of amyloid deposition in the cerebellum in Alzheimer's disease.
TL;DR: Differential vulnerability of the major components of microtubules was examined in ischemic gerbil brains by a light microscopic, immunohisto-chemical method using monoclonal antibodies for microtubule-associated protein (MAP) 1A and MAP2, polyclonal antibody for MAP1 and 2 as well as monoconal antibody for α-tubulin.
Abstract: Differential vulnerability of the major components of microtubules was examined in ischemic gerbil brains by a light microscopic, immunohistochemical method using monoclonal antibodies for microtubule-associated protein (MAP) 1A and MAP2, polyclonal antibody for MAP1 and 2 as well as monoclonal antibody for alpha-tubulin. Progressive cerebral ischemia during unilateral carotid occlusion for 5, 15 and 120 min and reperfusion for 3, 12 and 48 h following bilateral carotid occlusion for 10 min were studied. Ischemic lesions in the subiculum-CA1 region were visualized by all antibodies after ischemia for 5 min but the antibody for alpha-tubulin was less sensitive. The antibody for alpha-tubulin was also less sensitive than antibodies for MAPs for detection of early postischemic lesions. Differential sensitivity was also observed in the cerebral cortex and other brain regions. Microtubules in myelinated axons were more stable than those in dendrites. The observed loss of immunohistochemical reactivities for MAPs and alpha-tubulin may have been caused by activation of calcium-dependent proteolytic enzymes such as calpains. The discrepancy between MAPs and alpha-tubulin could be due to differences in affinities or topographic distributions of these proteins within microtubules.
TL;DR: The results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.
Abstract: Sixty-seven tumor specimens of epithelial choroid plexus neoplasms obtained by 60 biopsies and 7 autopsies from 52 patients were investigated. Diagnoses of the first operations were choroid plexus papilloma (PP; 32 cases), choroid plexus papilloma with histological atypies (atypical PP; 6 cases), and choroid plexus carcinoma (PC; 14 cases). Carcinoembryonic antigen was expressed by 2 of the 3 biopsies autoptically recognized as metastatic carcinomas and by 2 autopsy cases of PC, while it was absent in all biopsies of true choroid plexus tumors. Tumor cells positive for transthyretin (TTR, prealbumin), S-100 protein (S100), and glial fibrillary acidic protein (GFAP) were detected in 39, 46 and 13, respectively, of the 49 cases of true choroid plexus tumors. Fourth ventricle tumors expressed more S100 (number of positive tumor cells) than lateral ventricle tumors, PP more S100 and TTR than atypical PP/PC. Tumors from patients 20 years of age and older expressed more GFAP and TTR than tumors from younger patients. Of the 30 patients with complete follow-up 19 were alive 2 to 11 years after surgery, including 7 recurrencies. Eleven died from the tumor 4 months to 7 years after surgery. The following histopathologic features (in order of decreasing significance) were correlated with poor prognosis (recurrency or fatal outcome): less than 50% of the tumor cells heavily positive for S100, presence of mitoses, absence of TTR-positive cells, brain invasion by cell nests, absence of marked stromal edema, and presence of necrotic areas. Our results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.