Journal ArticleDOI
Life and Death of Neurons in the Aging Brain
John H. Morrison,Patrick R. Hof +1 more
TLDR
The qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored.Abstract:
Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.read more
Citations
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Journal ArticleDOI
Cortical areas abundant in extracellular matrix chondroitin sulphate proteoglycans are less affected by cytoskeletal changes in Alzheimer's disease.
TL;DR: It can be concluded that low susceptibility of neurons and cortical areas to neurofibrillary changes corresponds with high proportions of aggregating chondroitin sulphate proteoglycans in the neuronal microenvironment.
Journal ArticleDOI
Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent
Guy A. Higgins,Theresa M. Ballard,James N.C. Kew,J. Grayson Richards,John A. Kemp,Geo Adam,Thomas Johannes Woltering,Shigetada Nakanishi,Vincent Mutel +8 more
TL;DR: It is suggested that activation of mGlu2 receptors evokes a powerful inhibitory effect on hippocampal synaptic transmission and mGLU2 agonists produce a cognitive deficit consistent with this change, and that mGlam2 receptor antagonists may improve certain aspects of cognition and thus represent a novel approach for the symptomatic treatment of AD.
Journal ArticleDOI
Does Alzheimer's disease begin in the brainstem?
Goran Šimić,Gabrijela Stanić,Mihovil Mladinov,Nataša Jovanov-Milošević,Ivica Kostović,Patrick R. Hof +5 more
TL;DR: In this article, a novel pathogenetic scheme of Alzheimer's disease progression was proposed based on these findings of differential susceptibility and anatomical connectivity, and the authors speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD.
Journal ArticleDOI
Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease.
TL;DR: Investigation of the status of glutamatergic neurones in temporal, parietal and occipital cortices of patients with AD found changes were found to relate to the number of tangles in the temporal cortex, and there were no correlations with either mental test score or behaviour syndromes.
Journal ArticleDOI
Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: stereologic analysis of prefrontal cortex area 9.
Thierry Bussière,Panteleimon Giannakopoulos,Panteleimon Giannakopoulos,Constantin Bouras,Constantin Bouras,Daniel P. Perl,John H. Morrison,Patrick R. Hof +7 more
TL;DR: A stereologic analysis of a subset of pyramidal neurons known to be vulnerable in Alzheimer's disease and characterized by particularly high somatodendritic levels of nonphosphorylated neurofilament protein revealed that these particular neurons are far more likely to develop neurofibrillary tangles (NFT) and do so at a faster rate than other pyramid cells.
References
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Journal ArticleDOI
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Journal ArticleDOI
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Suzanne S. Mirra,Albert Heyman,Daniel W. McKeel,S. M. Sumi,Barbara J. Crain,L. M. Brownlee,Vogel Fs,James P. Hughes,van Belle G,Leonard Berg +9 more
TL;DR: The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects, which provides neuropathologic definitions of such terms as “definite Alzheimer's disease” (AD), “probable AD,” “possible AD” and “normal brain” to indicate levels of diagnostic certainty.