Although there have been significant advances in the identification of biomarkers of Alzheimer's disease (AD), comorbidity is a common finding at autopsy and the neuropathologic assessment at autopsy remains the gold standard for diagnosis.
The aims of the Neuropathology Core (Core D) will be: (1) To make neuropathologic diagnoses on all new brain accessions from HASD research participants using standard diagnostic criteria;(2) To perform brain autopsies and to collect, store at -80?C, and distribute formalin-fixed, paraffin-embedded, and frozen brain tissue samples to support HASD Projects and investigators and outside collaborations that enhance HASD research goals;(3) To support Projects 1 and 2 by providing a neuropathologic assessment and quantitative measures of the molecular pathology (beta- amyloidosis, tauopathy, synucleinopathy, and TDP-43 proteinopathy) of cases which come to autopsy. To support the Specific Aims of Project 3 by providing neuropathologic data, quantitative measures of the molecular pathology, and tissue (for mRNA and DNA extraction) relating to cases recruited for the study of genetic variants and their influence on the progression of AD (4) To maintain a computerized neuropathology database (CaTissue) in concert with the Biostatistics Core (Core C) and the Clinical Core (Core B) and the Washington University Neuroscience Blueprint Interdisciplinary Center Core (P30 NS057105). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi- quantitative morphometric data, neuropathology reports in collaboration with Dr. Perrin, bibliographic information, and data relevant to Core tissue banking activities. If acceptable, neuropathology data also will be transferred, after Biostatistics Core quality control and validation, to the National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA (U01 AG016976);(5) To undertake a developmental clinico-biomarker-neuropathologic study of HASD participants to determine the progression of biomarker changes in longitudinally assessed participants who transition from preclinical AD to symptomatic AD and who come to autopsy. Neuropathology will be the benchmark against which biomarker (CSF A?42 and pTau and PET-amyloid imaging) data will be assessed. With the Imaging and Biostatistics Cores and Projects 1 and 2, Core D will explore the contribution of AD biomarker changes with neuropathologic data including measures of A? and pTau burden, synaptic and neuronal loss.

Public Health Relevance

Core D: Neuropathology Project Narrative As instructed by the funding opportunity announcement for this application (PAR-13-329), only the Overall component contains a project narrative. Cores and projects were instructed not to include this section.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG003991-31A1
Application #
8739013
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (M1))
Project Start
Project End
2019-04-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
31
Fiscal Year
2014
Total Cost
$176,162
Indirect Cost
$57,823
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Maxwell, Taylor J; Corcoran, Chris; Del-Aguila, Jorge L et al. (2018) Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels. Alzheimers Res Ther 10:86
Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin et al. (2018) Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 14:205-214
Brainstorm Consortium (see original citation for additional authors) (2018) Analysis of shared heritability in common disorders of the brain. Science 360:
Kinnunen, Kirsi M; Cash, David M; Poole, Teresa et al. (2018) Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study. Alzheimers Dement 14:43-53
Ibanez, Laura; Dube, Umber; Davis, Albert A et al. (2018) Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease. Front Neurosci 12:230
Schultz, Stephanie A; Gordon, Brian A; Mishra, Shruti et al. (2018) Widespread distribution of tauopathy in preclinical Alzheimer's disease. Neurobiol Aging 72:177-185
Broce, Iris; Karch, Celeste M; Wen, Natalie et al. (2018) Correction: Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLoS Med 15:e1002504
Javaherian, Kavon; Newman, Brianne M; Weng, Hua et al. (2018) Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Dis Assoc Disord :
Liao, Fan; Li, Aimin; Xiong, Monica et al. (2018) Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation. J Clin Invest 128:2144-2155
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95

Showing the most recent 10 out of 911 publications