# Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2022 · $3,622,387

## Abstract

National Institute on Aging (NIA) Penn U19 “Center On Alpha-synuclein Strains In Alzheimer Disease &
Related Dementias”. Principal Investigator: John Q. Trojanowski
Center Summary/Abstract: This U19 Center pursues research priorities in the “Recommendations of the
Alzheimer's disease-related dementias conference”.13 It especially focuses on priorities that address
Alzheimer's disease (AD) and related dementias (ADRD) in topic areas of multiple etiology dementias, Lewy
body (LB) dementias (LBD), including dementia with LBs (DLB) and Parkinson's disease without (PD) and with
dementia (PDD), new guidelines on the biological definition of AD14-17 and reflects recommendations from a
recent NIA meeting on “Neurodegenerative Disease Transmissibility: Current Science and Recommendations
for Future Research” (Frosch M et al, in preparation, 2018). Among ADRD, AD with abundant LB co-pathology
is the most common subtype of AD. We hypothesize that accumulations of pathological aSyn lead to neuron
dysfunction and death due to misfolding and transmission of different strains of pathological aSyn to form LBs
and LNs and that aSyn and AD pathology interact to modify the distribution of each other and contribute to
behavioral impairments. To accomplish these goals, Projects I and II complement each other and Projects III
and IV by seeking to elucidate aSyn strains underlying AD+aSyn/LBD compared to PD, Multiple system
atrophy (MSA) is studied as a control because it is characterized by aSyn glial cytoplasmic inclusions (GCIs)
that are comprised of a distinct aSyn strain which is more potent than LBD or AD+aSyn strains of pathological
aSyn. In parallel, Project III analyzes regional AD/LBD neuropathology with novel monoclonal antibodies
(mAbs) to correlate these data with diverse cognitive difficulties and structural imaging. A 2X2 design is used
that contrasts clinical AD phenotypes and primary AD pathologies. This is complemented by Project IV which
measures cognition, blood and cerebrospinal (CSF) biomarkers, including aSyn, as well as SNP arrays, to
better understand, diagnose and manage diverse clinical manifestations of AD/LBD in order to advance
towards a precision medicine approach for care and disease management. The landmark discoveries of aSyn
gene (SNCA) alterations pathogenic for LBD and that pathological aSyn is the disease protein in
synucleinopathies, in addition to the cell-to-cell spread of aSyn strains, places aSyn at center stage for
understanding mechanisms of AD+aSyn and LBD. This Penn U19 Center addresses these key issues in four
Projects supported by four Cores. Moreover, this Center also will work with NIA to provide biofluids, DNA/RNA,
autopsy tissue and data collected from ADRD patients over the past 20 years at Penn in addition to aSyn
strains to qualified investigators. By addressing the hypothesis that distinct aSyn strains underlie
AD+aSyn/LBD, we will clarify the molecular basis of heterogeneity in AD+aSyn/LBD while opening up new
t...

## Key facts

- **NIH application ID:** 10452557
- **Project number:** 5U19AG062418-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** VIRGINIA M LEE
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,622,387
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452557

## Citation

> US National Institutes of Health, RePORTER application 10452557, Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias (5U19AG062418-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10452557. Licensed CC0.

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