The Neuropathology Core C will provide neuropathologic diagnostic service for all program project subjects who come to autopsy. The CERAD neuropathology protocol will be used to assess general neuropathogic findings. The NIA/AARP quantitative diagnostic criteria will be used to establish a pathologic diagnosis of Alzheimer's disease (AD). The Core will use quantitative manual and automated computer-assisted morphometric methods to determine patterns, prevalence and severity of neuron atrophy and loss and NP and NFT accumulation associated with aging, AD, and AD-associated with Parkinsonism. Multivariate statistics will be used to correlate pathologic lesions with clinical and psychometric measures, especially important in mild dementia. The Core will process an estimated 25 brains annually. We will provide neuropathologic documentation of specific lesions and diseases in our aging and demented and nondemented aged samples. WE will provide the data for validation of clinical diagnostic criteria for subjects in Project 1 (intellectual function and Alzheimer changes in the very old), Project 3 (SDAT and Parkinsonism), Project 4 (memory processing in aging and dementia), Project 5 (lay interviewer assessment), Project 7 (neuroanatomical markers), and Project 8 (PET in aging and SDAT). Histologic criteria for differentiation of healthy aging and AD in the very old will be clarified. The neuropathological basis of parkinsonism in AD will be clarified. The hypothesis that parkinsonian dementia is due to SDAT-like neuropathology will be tested. By studying cases of mild SDAT and counting neuritic plaques by subtypes, we will test the additional hypothesis that purely fibrillary plaques are precursors to classical plaques with expanded neurites and amyloid cores. Our studies will identify how hippocampal, basal forebrain and neocorticallesions are related to dementia in AD. The relevant material for this effort includes those healthy control subjects enrolled in the Clinical Core who come to autopsy in the stages of very mild dementia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG003991-07
Application #
3090778
Study Section
Aging Review Committee (AGE)
Project Start
1984-01-01
Project End
1993-12-31
Budget Start
1990-01-02
Budget End
1990-12-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Armstrong, Richard A; McKee, Ann C; Stein, Thor D et al. (2018) Cortical degeneration in chronic traumatic encephalopathy and Alzheimer's disease neuropathologic change. Neurol Sci :
Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G et al. (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 98:861-864
Deming, Yuetiva; Li, Zeran; Benitez, Bruno A et al. (2018) Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease? Expert Opin Ther Targets 22:587-598
Millar, Peter R; Balota, David A; Bishara, Anthony J et al. (2018) Multinomial models reveal deficits of two distinct controlled retrieval processes in aging and very mild Alzheimer disease. Mem Cognit 46:1058-1075
Musiek, Erik S; Bhimasani, Meghana; Zangrilli, Margaret A et al. (2018) Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol 75:582-590
Vlassenko, Andrei G; Gordon, Brian A; Goyal, Manu S et al. (2018) Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease. Neurobiol Aging 67:95-98
Broce, Iris; Karch, Celeste M; Wen, Natalie et al. (2018) Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLoS Med 15:e1002487
Stout, Sarah H; Babulal, Ganesh M; Ma, Chunyu et al. (2018) Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers. Alzheimers Dement 14:610-616
Aschenbrenner, Andrew J; Gordon, Brian A; Benzinger, Tammie L S et al. (2018) Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology 91:e859-e866
Day, Gregory S; Musiek, Erik S; Morris, John C (2018) Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions. Alzheimer Dis Assoc Disord 32:291-297

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