# Vascular MicroRNA-212 in CAA and Alzheimer's disease

> **NIH NIH R21** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $66,253

## Abstract

Supplement Summary and Aims
The funded grant aims to determine the role of microRNAs (miRNAs) in post-
transcriptional regulation in the context of cerebrovascular dysfunction and blood-brain-
barrier (BBB) disruption, particularly within Alzheimer's disease (AD) and cerebral
amyloid angiopathy (CAA). AD is characterized by an accumulation of amyloid-β (Aβ)
plaques and neurofibrillary tangles, with cerebrovascular dysfunction (CVD) and
neuroinflammation playing key roles in the progression of the disease. In fact, most cases
of AD exhibit Aβ deposition in and around cerebral blood vessels, thus presenting an
additive effect to the pathology of the disease.
The BBB, composed mainly of endothelial cells (ECs), regulates the entry of circulating
substances from the blood to the brain and assists in clearing harmful molecules from the
brain, including oligomeric Aβ. Disruption of the BBB and the accumulation of Aβ in and
around cerebral blood vessels is associated with changes in ECs, yielding a
proinflammatory phenotype and leading to apoptosis. In our preliminary data of the parent
grant, we have found that miRNA-212 is decreased in ECs treated with Aβ. Previously,
we have shown that Aβ treatment leads to EC apoptosis and increase in EC barrier
permeability. We have shown in our preliminary data that several genes involved in EC
apoptosis contain binding sequences for miRNA-212.
Our overarching goal is to test the hypothesis that Aβ promotes cerebrovascular
dysfunction and BBB failure via endothelial cell miRNA-212.
To achieve our goal, during this Supplement I specifically aim to accomplish the following
Aims. Aim 1: measure miR-212 levels in exosomes released from ECs under the same
Aβ conditions as in Aim 1 of the Grant. The release of miRNAs via exosomes may be
essential for regulation in nearby cells of the neurovascular unit and may serve as a
biomarker for AD and CAA diagnosis and progression. Aim 2: assess the impact of miR-
212 downregulation and rescue on BBB permeability in neurovascular unit complex
systems. To ascertain the role of miRNA in CVD and BBB loss of function.

## Key facts

- **NIH application ID:** 11089959
- **Project number:** 3R21NS135606-01S1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Silvia Fossati
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $66,253
- **Award type:** 3
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089959

## Citation

> US National Institutes of Health, RePORTER application 11089959, Vascular MicroRNA-212 in CAA and Alzheimer's disease (3R21NS135606-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11089959. Licensed CC0.

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