# Core D: Neuropathology Core

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2021 · $441,690

## Abstract

Core D: Neuropathology Project Summary
Mounting evidence suggests that Alzheimer disease (AD) pathology – which includes amyloid plaques (made
of beta-amyloid peptide), neurofibrillary tangles (made of tau protein), and loss of synapses within the brain –
begins decades before the onset of cognitive symptoms, during a 'preclinical' phase of AD. Data from
epidemiological and genetic studies additionally suggest that these pathological changes - and the risk of
developing dementia - may be influenced by many factors, including race, sleep, and numerous genetic traits.
To meet the goals of the National Alzheimer's Project Act, it will be essential to (1) understand these
demographic, behavioral and genetic factors, (2) expand our capacity to detect different aspects and different
stages of AD pathology in living individuals, and (3) improve our ability to detect and monitor subtle changes in
cognitive function for early diagnosis and the evaluation of treatment effectiveness in clinical trials.
In this effort, studies of biofluids and postmortem brain tissue are indispensable. By measuring the levels of
beta-amyloid and tau proteins in cerebrospinal fluid (CSF), we can now determine with high accuracy whether
living participants have significant AD pathology, even before they show symptoms. This information enables
us to enroll cognitively normal participants with or without AD pathology into studies, laying the groundwork to
develop new tests, to discover unknown risk factors, and to unravel the mysteries behind known risk factors for
AD pathology and subsequent AD dementia. In complementary fashion, comprehensive brain examination can
establish not only whether a person had AD, but also other neurodegenerative diseases (e.g., Lewy body
disease, frontotemporal lobar degeneration, vascular dementia). Finally, studies of these specimens,
themselves, can reveal new secrets about the pathophysiology of AD.
The mission of the Heathy Aging and Senile Dementia (HASD) Neuropathology Core (NPC) is to collect,
process, analyze, store, and distribute plasma, CSF, and autopsy brain tissue from study participants to support
the scientific projects of the HASD Program Project, and other scientific projects around the world. Towards this
end, the NPC will measure CSF A40, A42, tau, p-tau181, and synaptic/neuronal markers (neurogranin,
SNAP-25 and neurofilament light chain), and will also examine brains for neuronal loss, gliosis, vasculopathy,
infarcts, white matter pallor, and deposits of A, hyperphosphorylated tau, alpha-synuclein, and pTDP-43. In
support of HASD Projects, these data will: be analyzed for differences between African American and mon-
Hispanic white participants (Project 1); evaluate associations of AD pathology and sleep parameters (Project
2); help to identify novel genetic modifiers promoting cognitive reserve and resilience in the presence of AD
pathology (Project 3); inform analysis of data from a smartphone application for measuring sub...

## Key facts

- **NIH application ID:** 10131741
- **Project number:** 5P01AG003991-38
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** RICHARD Justin PERRIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,690
- **Award type:** 5
- **Project period:** 1997-01-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131741

## Citation

> US National Institutes of Health, RePORTER application 10131741, Core D: Neuropathology Core (5P01AG003991-38). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131741. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*