The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

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The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

Neuropathological stageing of Alzheimer-related changes.

It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer9s disease (AD) may be caused by deposition of amyloid β-peptide (Aβ) in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Aβ in the brain is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Aβ production and Aβ clearance.

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The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics

Staging of brain pathology related to sporadic Parkinson’s disease

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

The cerebellar cortex of progressive supranuclear palsy (PSP) cases exhibited a characteristic pathology which occurred neither in healthy aged individuals nor in cases of fully developed Alzheimer’s disease. All of the 11 PSP cases studied reveal altered mossy fiber excrescences containing abnormal and hyperphosphorylated tau protein. Moreover, this abnormal material also appeared in cerebellar oligodendrocytes. Accordingly, there is not only the destruction of the cerebellar output system, which is already known, but also the involvement of the cerebellar input system.

Mossy fiber involvement in progressive supranuclear palsy

Drs. Heinsen and Grinberg suggest that because of sampling bias and insufficient sensitivity of the tau seeding assay, our methods miss “hidden” seeding activity in the locus coeruleus (LC) at early stages of Alzheimer’s disease (AD), and that our conclusion that the LC is unlikely to be the origin of pathological seeding in AD is incorrect. We strongly disagree, and would like to make several points.

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Rebuttal to Drs. Grinberg and Heinsen.

Alzheimer pathogenesis for men and women

BACKGROUND Flail arm syndrome is a restricted phenotype of motor neuron disease that is characterized by progressive, predominantly proximal weakness and atrophy of the upper limbs. OBJECTIVE The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from flail arm syndrome patients using a hypothesis-guided tract-of-interest-based approach to identify in vivo microstructural changes according to a neuropathologically defined amyotrophic lateral sclerosis (ALS)-related pathology of the cortico-efferent tracts. METHODS DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the neuropathological ALS-propagation pattern for 43 flail arm syndrome patients vs 43 'classical' ALS patients vs 40 matched controls. RESULTS The analysis of white matter integrity demonstrated regional FA reductions for the flail arm syndrome group predominantly along the CST. In the tract-specific analysis according to the proposed sequential cerebral pathology pattern of ALS, the flail arm syndrome patients showed significant alterations of the specific tract systems that were identical to 'classical' ALS if compared to controls. CONCLUSIONS The DTI study including the tract-of-interest-based analysis showed a microstructural involvement pattern in the brains of flail arm syndrome patients, supporting the hypothesis that flail arm syndrome is a phenotypical variant of ALS.

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Involvement of cortico-efferent tracts in flail arm syndrome: a tract-of-interest-based DTI study.

Der Morbus Parkinson ist eine stetig voranschreitende degenerative Erkrankung des zentralen, peripheren und enterischen Nervensystems des Menschen. Im Verlauf der Erkrankung erleiden neben der Substantia nigra eine Reihe von extranigralen Komponenten des motorischen Systems sowie zahlreiche Zentren des limbischen Systems und der autonomen Regulation schwerwiegende Zerstorungen. Der Morbus Parkinson ist daher eine Multisystemerkrankung. Nur bestimmte Arten von Projektionsneuronen entwickeln die fur die Erkrankung charakteristischen Veranderungen des neuronalen Zytoskeletts. Das Ergebnis dieser Veranderungen sind intraneuronale Einschlusskorper in Form von Lewy-Korpern in den Zellleibern und Lewy-Neuriten in den Zellfortsatzen, die zum vorzeitigen Absterben der betroffenen Nervenzellen fuhren. Aufgrund der selektiven neuronalen Vulnerabilitat ergibt sich eine charakteristische Verteilung der Veranderungen innerhalb des Nervensystems mit entsprechenden Einbusen der Funktionsfahigkeit zahlreicher Systeme.

Neuroanatomie des Morbus Parkinson Veränderungen des neuronalen Zytoskeletts in nur wenigen für den Krankheitsprozess empfänglichen Nervenzelltypen führen zur progredienten Zerstörung umschriebener Bereiche des limbischen und des motorischen Systems

Heiko Braak

Papers

Mossy fiber involvement in progressive supranuclear palsy

Rebuttal to Drs. Grinberg and Heinsen.

Alzheimer pathogenesis for men and women

Involvement of cortico-efferent tracts in flail arm syndrome: a tract-of-interest-based DTI study.

Neuroanatomie des Morbus Parkinson Veränderungen des neuronalen Zytoskeletts in nur wenigen für den Krankheitsprozess empfänglichen Nervenzelltypen führen zur progredienten Zerstörung umschriebener Bereiche des limbischen und des motorischen Systems