# Project II "aSyn Strains & Diverse Synucleinopathies"

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2020 · $456,561

## Abstract

PROJECT II: Pathologic Alpha-synuclein Strains & Diverse Synucleinopathies
Project II Leader: J.Q. Trojanowski; Co-Investigators: V.M.-Y. Lee & K. Luk
Project II Summary/Abstract
 Project II (formerly Project IV and renumbered II to improve the flow of the research) in this new U19
“Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias” at the University of
Pennsylvania (Penn) Perelman School of Medicine (PSOM) tests the hypothesis that heterogeneity and
progression of alpha-synuclein (aSyn) pathology in Lewy bodies (LBs) and neurites (LNs) of Parkinson's
disease without (PD) or with dementia (PDD) and dementia with LBs (DLB), as well as Alzheimer's disease
(AD) with aSyn (AD+aSyn) LBs and LNs co-pathologies represent the spread of different neuronal aSyn
strains.1 We compare these strains to each other and with aSyn strains from multiple system atrophy (MSA)
glial cytoplasmic inclusions (GCI) which rarely appear in AD or in combination with LBs/LNs. This will advance
insights into how distinct aSyn strains in AD+aSyn vs PD vs PDD vs DLB vs MSA drive clinical and
pathological heterogeneity of these disorders. Since dementia in PDD and DLB, referred to as LB dementia
(LBD), frequently is accompanied by AD co-pathologies, including Aβ amyloid plaques and neurofibrillary tau
inclusions, and 50% of AD patients have LBs, we also test the hypothesis that aSyn strains in PDD vs DLB vs
AD+aSyn brains induce Aβ and tau pathologies whereas aSyn strains in PD vs MSA brains lacking AD
pathology might not. Project II collaborates with Project I, which performs in vitro aSyn strain studies and
provides Project II with highly characterized and validated aSyn strains from postmortem AD+aSyn, PD, LBD
and MSA brains as well as in vitro amplified LB and GCI aSyn strains. For these studies, living subjects are
studied in Core B and Projects III/IV and their brains are obtained through Core C while Core D provides data
management, biostatistics and bioinformatics support. The extent to which the models of synucleinopathies
induced by intracerebral injections of LB and GCI aSyn strains in Project II correspond to authentic human
AD+aSyn vs PD vs LBD vs MSA will be assessed. Thus, Project II works closely with all U19 Center
Cores/Projects to determine if the LB aSyn strain (aSyn-LB) from PD vs AD+aSyn vs LBD brains compared to
the MSA GCI aSyn strain (aSyn-GCI) differentially induce pathological aSyn in neurons versus glia as well as
recruit AD-like Aβ and tau deposits or other neurodegenerative disease co-pathologies such as TDP-43. This
will be done following intracerebral injections of these aSyn strains into wild type (WT) mice, human WT aSyn
transgenic (Tg) mice (line 61) on a mouse aSyn knock out (KO) background (KO61) and CNP-aSyn (M2) Tg
mice with an aSyn KO background (KOM2) that model GCIs compared to Tg mouse models of AD-like Aβ
plaques (5xFAD, Tg2576, APP knock in mice) and a Tg mouse model of AD-like tau pathologies (PS19 line).
The ...

## Key facts

- **NIH application ID:** 10020335
- **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:** $456,561
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020335

## Citation

> US National Institutes of Health, RePORTER application 10020335, Project II "aSyn Strains & Diverse Synucleinopathies" (5U19AG062418-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10020335. Licensed CC0.

---

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