# Neuropathology, Biomarker & Genetics Core C

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2020 · $415,614

## Abstract

CORE: Neuropathology, Biomarker & Genetics Core C
Core Leader: John Q. Trojanowski; Co-Core Leaders: Alice Chen-Plotkin, Edward B. Lee and Vivianna
Van Deerlin
Core Summary/Abstract
The Neuropathology, Biomarker and Genetics Core C in this NIA U19 “ Center On Alpha-synuclein Strains
In Alzheimer Disease & Related Dementias” at the University of Pennsylvania (Penn) Perelman School of
Medicine (PSOM) banks and characterizes postmortem brain tissue collected from clinically assessed
Alzheimer's disease (AD) patients as well as Parkinson's disease (PD) patients without and with cognitive
impairments (CI) or dementia (PDD) and dementia with Lewy body (DLB) patients followed in Core B and
studied in Projects I-IV. It also collects plasma, cerebrospinal fluid (CSF) and DNA from these subjects,
performs genotyping, and handles genotyping data. PD, PDD and DLB (referred to as Lewy body disorders or
LBD) as well as multiple system atrophy (MSA) are a spectrum of synucleinopathies characterized by alpha-
synuclein (aSyn) aggregates in neurons referred to as Lewy bodies (LBs) and Lewy neurites (LNs) in
PD/PDD/DLB or as glial cytoplasmic inclusions (GCIs) in oligodendrocytes of MSA. LBs are the most common
co-pathology in AD while AD and LBD are the most common aging related neurodegenerative dementias.
Recent findings suggest that progression of AD with aSyn pathology (AD+aSyn) and LBD could reflect the cell-
to-cell spread of pathological aSyn conformers or strains in the nervous system followed by progressive
neurodegeneration and there is evidence that tau and aSyn cross-fibrillize each other. Thus, this U19 focuses
on the progression of AD+aSyn and LBD as well as mechanisms of CNS cell-to-cell spread of pathological
aSyn. Projects I and II showed that MSA may result from a unique aSyn GCI strain (aSyn-GCI strain) that
spreads among oligodendroglial cells and is distinct from those aSyn conformers linked to LBs/LNs in neurons
of LBD (aSyn-LB strain). Hence, Core C will work closely with Projects I and II wherein distinct strains of
pathological aSyn will be analyzed and their features will subsequently be associated with phenotypic,
biomarker and genetic patient data in collaboration with Projects III and IV. Core C supports the U19 Center
goals by implementing postmortem diagnostic criteria for AD/LBD patients referred for autopsy from Core B,
collecting biosamples from these patients and assessing the utility of antemortem diagnostics including studies
of potential genetic and biomarker signatures. Core C works closely with all Cores/Projects to support the
Center's mission by improving diagnostic methods, and providing samples of brain tissue, biofluids and DNA to
investigators within and beyond the Penn U19 Center.

## Key facts

- **NIH application ID:** 10020332
- **Project number:** 5U19AG062418-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JOHN Q. TROJANOWSKI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,614
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020332

## Citation

> US National Institutes of Health, RePORTER application 10020332, Neuropathology, Biomarker & Genetics Core C (5U19AG062418-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020332. Licensed CC0.

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