# Dominantly Inherited Alzheimer Network: Neuropathology

> **NIH NIH U19** · WASHINGTON UNIVERSITY · 2021 · $223,233

## Abstract

Core D: Neuropathology PROJECT SUMMARY
Mounting evidence suggests that Alzheimer disease (AD) pathology begins decades before the onset of
cognitive symptoms, during a 'preclinical' phase. The changes that occur in the brain over the entire course of
AD, from the preclinical phase through dementia, are complex; they involve the deposition of amyloid-beta
peptide into microscopic plaques, a reactive inflammatory response within the brain (‘neuroinflammation’), the
formation of neurofibrillary tangles within neurons, and the loss of neurons and their connections (synapses).
Within the last decade, building on our advancing knowledge of AD, several ‘biomarkers’ (biofluid analyses and
neuroimaging techniques) have been developed to test for and monitor the course of these changes, and these
‘biomarkers’ have been applied in clinical trials seeking to evaluate the effectiveness of treatments that target
the changes seen in AD. But much about AD remains poorly understood. A better understanding of the disease
– and better ‘biomarkers’ – will hasten progress towards an effective treatment for AD.
In this effort, studies of postmortem brain tissue are indispensable. Comprehensive brain examination can
establish not only whether a person had AD and how advanced that AD pathology had become, but can also
detect other neurodegenerative diseases that commonly coincide with AD. Just as important: scientific studies
of postmortem brain specimens can facilitate the evaluation of new neuroimaging biomarker compounds in
ways that are not possible in living participants, and can reveal new secrets about the pathophysiology of AD.
The mission of the Dominantly Inherited Alzheimer Network (DIAN) Neuropathology Core (NPC) is to collect,
process, analyze, store, and distribute autopsy brain tissue from study participants to support the scientific
projects of DIAN, and other scientists around the world. Towards this end, the NPC examines brains for the
amounts and distributions of neuronal loss, gliosis, vascular disease sequela, and deposits of A,
hyperphosphorylated tau, alpha-synuclein, and pTDP-43. These detailed studies enable us to provide
appropriate neuropathologic diagnoses to families, and supply appropriate tissues to scientific studies.
By providing tissue samples and histopathological data to current DIAN Projects, the NPC will help to: improve
our understanding of the atomic structures of the forms of amyloid-beta peptide that appear in AD brain tissue
(Project 1); study the impact of different ADAD mutations on the autoradiographic binding patterns of amyloid
PET tracer PIB (Project 1); evaluate and compare the autoradiographic binding patterns of tau PET tracers AV-
1451 and MK-6240 (Project 2); and study the complex systems biology of AD (including changes in neurons
and glial cells, neuroinflammation, and synaptic loss) using cutting-edge proteomic and molecular techniques
(Project 3). Collectively, the findings from these studies will inform the sel...

## Key facts

- **NIH application ID:** 10225481
- **Project number:** 5U19AG032438-10
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** RICHARD Justin PERRIN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,233
- **Award type:** 5
- **Project period:** 2008-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225481

## Citation

> US National Institutes of Health, RePORTER application 10225481, Dominantly Inherited Alzheimer Network: Neuropathology (5U19AG032438-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225481. Licensed CC0.

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