# Uncovering BIN1 functions in myelin-producing oligodendrocytes

> **NIH NIH R21** · TEXAS A&M UNIVERSITY · 2021 · $402,526

## Abstract

PROJECT SUMMARY
Myelin is essential to rapid axonal impulse propagation and long-term integrity and survival of axons. Cerebral white
matter alterations are common early features in late-onset Alzheimer’s disease brains, yet the cellular basis for these
changes, long before the formation of senile plaques and Tau-containing neurofibrillary tangles, remains largely
unexplored. Large unbiased transcriptome studies recently revealed alterations in myelination and axonal integrity at
the early stage of Alzheimer’s disease, suggesting potential contributions of myelin-producing oligodendrocytes to AD
pathogenesis. Interestingly, the second most prevalent genetic risk factor for late-onset Alzheimer’s disease, BIN1, is
primarily expressed by mature oligodendrocytes. However, essentially nothing is known about BIN1 functions in
oligodendrocytes under physiological or pathophysiological conditions. Our preliminary data suggest that BIN1 protein is
distributed at discrete locations in the cytoplasmic channels of uncompact myelin and interacts with phosphorylated Tau
along axon with early Tau pathology. Because oligodendrocyte uses cytoplasmic channels to connect soma to distant
peripheral processes that enwrap and interact with the axon, and because BIN1 plays a role in vesicle sorting,
membrane remodeling and endocytosis, we hypothesize that BIN1 functions in oligodendrocyte and axon
communication and in long-term maintenance of the integrity of the myelin-axon unit. In this R21 proposal, we will
determine (1) the functional role of BIN1 in oligodendrocyte myelination and the maintenance of
oligodendrocyte/myelin-axonal integrity using oligodendrocyte-specific BIN1 conditional knockout mice; and (2) the
contribution of oligodendrocyte-expressing BIN1 in modulating axonal Tau pathology using a transgenic murine model
that expresses human mutant Tau. Understanding BIN1-associated cellular pathways will likely provide new insights into
how this risk factor might relate to the onset and/or progression of late-onset Alzheimer’s disease and related
dementias.

## Key facts

- **NIH application ID:** 10214226
- **Project number:** 1R21AG072479-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** JIANRONG LI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,526
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214226

## Citation

> US National Institutes of Health, RePORTER application 10214226, Uncovering BIN1 functions in myelin-producing oligodendrocytes (1R21AG072479-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10214226. Licensed CC0.

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