Journal ArticleDOI
Evolution of the neuropathology of Alzheimer's disease
Heiko Braak,Eva Braak +1 more
TLDR
The most conspicuous changes seen in the brain are deposits of insoluble proteins in both extracellular and intraneuronal locations, which correlates with the gradual worsening of clinical symptoms in Alzheimer's disease.Abstract:
Our knowledge of the etiology and pathogenesis of Alzheimer's disease is limited. The most conspicuous changes seen in the brain are deposits of insoluble proteins in both extracellular and intraneuronal locations. The extracellular deposits consist primarily of a specific A4 amyloid protein. The significance of these deposits remains to be determined, as they are often found in the cerebral cortex of non-demented elderly persons. More telling is the gradual accumulation of insoluble fibrous material within some neurons that consists mainly of abnormally phosphorylated tau protein. Six stages of increasingly severe cortical destruction can be distinguished. Stages I and II are characterized by neurofibrillary changes that are largely confined to the transentorhinal region, whereas stages III and IV are marked by severe involvement of both the entorhinal and transentorhinal regions. Isocortical destruction occurs during stages V and VI. This progression in cortical pathology correlates with the gradual worsening of clinical symptoms.read more
Citations
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Journal ArticleDOI
Normal Cognitive Aging
TL;DR: The neurocognitive changes observed in normal aging are described, followed by a description of the structural and functional alterations seen in aging brains.
Journal ArticleDOI
Ageing as a risk factor for neurodegenerative disease.
Yujun Hou,Xiuli Dan,Mansi Babbar,Yong Wei,Steen G. Hasselbalch,Deborah L. Croteau,Vilhelm A. Bohr,Vilhelm A. Bohr +7 more
TL;DR: Hallmarks of ageing — genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication — correlate with susceptibility to neurodegenerative disease.
Journal ArticleDOI
Use of Florbetapir-PET for Imaging β-Amyloid Pathology
Christopher M. Clark,Julie A. Schneider,Barry J. Bedell,Thomas G. Beach,Warren B. Bilker,Mark A. Mintun,Michael J. Pontecorvo,Franz Hefti,Alan Carpenter,Matthew Flitter,Michael J. Krautkramer,Hank F. Kung,R. Edward Coleman,P. Murali Doraiswamy,Adam S. Fleisher,Marwan N. Sabbagh,Carl H. Sadowsky,Eric M. Reiman,Simone P. Zehntner,Daniel Skovronsky +19 more
TL;DR: Evidence is provided that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life and for the prediction of progression to dementia.
Journal ArticleDOI
Quantitative gait dysfunction and risk of cognitive decline and dementia
TL;DR: The findings indicate that quantitative gait measures predict future risk of cognitive decline and dementia in initially non-demented older adults.
Journal ArticleDOI
Verbal fluency performance in dementia of the Alzheimer's type: a meta-analysis.
TL;DR: The semantic memory deficit in DAT qualifies as a differential deficit, but executive dysfunction as indexed by phonemic fluency does not constitute an additional isolated feature of the disorder.
References
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Journal ArticleDOI
Neuropathological stageing of Alzheimer-related changes.
Heiko Braak,Eva Braak +1 more
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Journal ArticleDOI
Distributed Hierarchical Processing in the Primate Cerebral Cortex
TL;DR: A summary of the layout of cortical areas associated with vision and with other modalities, a computerized database for storing and representing large amounts of information on connectivity patterns, and the application of these data to the analysis of hierarchical organization of the cerebral cortex are reported on.
Journal ArticleDOI
Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans.
TL;DR: The role of the hippocampus is considered, which is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.
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.
Journal ArticleDOI
Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology
Inge Grundke-Iqbal,Khalid Iqbal,Yunn-Chyn Tung,Maureen Quinlan,Henryk M. Wisniewski,Lester I. Binder +5 more
TL;DR: It is suggested that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF, the two major locations of paired-helical filaments in Alzheimer disease brain.