# CAA, Tau and Neurodegeneration

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $534,813

## Abstract

SUMMARY
Alzheimer disease (AD), the most common form of dementia, is characterized by the extracellular deposition of
parenchymal and vascular ß-amyloid (Aß), intracellular accumulation of tau as neurofibrillary tangles (NFTs),
neuronal cell loss, and significant inflammation1,2. During the past decades, a major focus of research has been
the understanding of the connection between parenchymal Aß, NFT, and neurodegeneration, with the
contribution of vascular pathology to NFT and neurodegeneration remaining under studied. Cerebral amyloid
angiopathy (CAA) is typified by the cerebrovascular deposition of Aß and has a close molecular relationship with
AD. Unfortunately, there is no clear understanding of the molecular and cellular mechanisms and targets that
underlie the contribution of CAA to neurodegeneration and dementia. Therefore, the main goal of this
proposal is to dissect the mechanism(s) by which CAA leads to neuroinflammation, abnormal
tau accumulation, and neurodegeneration. CAA has been associated to an active immune response and
perivascular deposition of hyperphosphorylated tau; yet these three pathological entities have never been linked
in a spatio-temporal context in relation to cognitive decline. Hence, we propose to determine if a disease-
associated form of tau, catalyzed by a pro-inflammatory response, plays a major role on behavioral deficit and
the synaptotoxicity observed in dementias associated to CAA, using a well-established genetic mouse model for
CAA (Tg-FDD)12. We will also determine if the triggering receptor expressed on myeloid cells 2 (TREM2) plays
a preponderant role in vascular amyloid deposition and vascular integrity in vivo during CAA progression.
Furthermore, we will identify the potential role of tau on CAA and subsequent neurotoxicity by determining if
the ablation of functional endogenous tau suppresses behavioral deficit and toxicity in our genetic mouse model
for CAA. The proposed studies will provide a platform for the understanding of the role of CAA in
neurodegeneration. Information gained from these studies might lead to the development of effective
therapeutics not only for CAA and AD, but also for a number of neurodegenerative diseases characterized by the
vascular accumulation of amyloid peptides.

## Key facts

- **NIH application ID:** 10397996
- **Project number:** 5R01AG059639-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Cristian Lasagna-Reeves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $534,813
- **Award type:** 5
- **Project period:** 2018-08-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397996

## Citation

> US National Institutes of Health, RePORTER application 10397996, CAA, Tau and Neurodegeneration (5R01AG059639-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10397996. Licensed CC0.

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