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
Clinical validity of Braak neuropathological staging in the oldest-old.
G. Gold,Constantin Bouras,E. Kövari,Alessandra Canuto,B. González Glaría,A. Malky,Patrick R. Hof,Jean-Pierre Michel,Panteleimon Giannakopoulos +8 more
TL;DR: The present data suggest that the substantial involvement of the hippocampus which characterizes Braak stage IV is a key step in the development of overt clinical signs of dementia in the oldest-old and indicate that Braak staging represents a broad concept of the evolution of neurofibrillary tangles rather than a precise hierarchical model associated with a stepwise deterioration of cognitive abilities near the upper limit of life.
Journal ArticleDOI
Calpain Mediates Calcium-Induced Activation of the Erk1,2 MAPK Pathway and Cytoskeletal Phosphorylation in Neurons: Relevance to Alzheimer's Disease
Veeranna,Takahide Kaji,Barry Boland,Barry Boland,Tatjana Odrljin,Panaiyur S. Mohan,Panaiyur S. Mohan,Balapal S. Basavarajappa,Corrinne M. Peterhoff,Anne M. Cataldo,Anne M. Cataldo,Anna Rudnicki,Niranjana D. Amin,Bing Sheng Li,Harish C. Pant,Basalingappa L. Hungund,Ottavio Arancio,Ottavio Arancio,Ralph A. Nixon,Ralph A. Nixon +19 more
TL;DR: Using immunochemistry, Western blot analysis, and kinase activity measurements, the authors demonstrate that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain.
Journal ArticleDOI
Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease
Isak Prohovnik,Daniel P. Perl,Kenneth L. Davis,Leslie S. Libow,Gerson T. Lesser,Vahram Haroutunian +5 more
TL;DR: The nature or expression of Alzheimer disease may be different in severely demented older patients, who have equal cholinergic deficits but significantly lower plaque and tangle burden.
Journal ArticleDOI
Estrogen therapy: is time of initiation critical for neuroprotection?
TL;DR: More definitive evidence is needed to confirm that the early initiation of estrogen therapy that is continued for a few years provides enduring protection against cognitive aging 15−20 years later.
Journal ArticleDOI
Predictors of mortality in patients with Alzheimer’s disease living in nursing homes
Giovanni Gambassi,Francesco Landi,Kate L. Lapane,Antonio Sgadari,Vincent Mor,Roberto Bernabei +5 more
TL;DR: Age, sex, functional limitation, and malnutrition seem to be the strongest predictors of death for patients with Alzheimer’s disease in nursing homes, and minority groups were less likely to die relative to white people.
References
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Journal ArticleDOI
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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.