# FAM222A and amyloid plaque deposition in Alzheimer's Disease

> **NIH NIH RF1** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $1,013,931

## Abstract

PROJECT SUMMARY
Alzheimer's disease (AD) is the leading cause of dementia in the elderly, characterized by neurofibrillary
tangles, senile plaques and a progressive loss of neuronal cells in neocortex and hippocampus. Currently,
there is no effective treatment for AD. Less than 10% of AD cases are early onset with only a small fraction
caused by autosomal dominantly inherited genetic changes in APP, presenilin 1 (PS1) or presenilin 2 (PS2), all
of which are responsible for the overproduction of Aβ and the earlier formation of amyloid plaques. Though
more than 90% of AD cases are referred to as sporadic AD without family history, they have the similar clinical
and pathologic phenotypes as sporadic AD. Despite a large body of evidence suggests that Aβ deposition in
the brain as the likely culprit playing a critical role in the pathogenesis of AD or related dementia, the molecular
pathomechanisms of amyloid plaque formation remain largely elusive. Interestingly, in our recent study, we
have identified a novel protein Aggregatin specifically accumulated within the centers of amyloid plaques.
Aggregatin is predominantly expressed in the central nervous system and increased in brains of patients with
AD or amyloid precursor protein (APP) transgenic mice for AD. Excitingly, Aggregatin physically interacts with
Aβ with very high affinity, and remarkably facilitates Aβ aggregation even under near-physiologic nanomolar
concentrations. Forced expression of Aggregatin resulted in increased amyloid deposition, whereas ablation of
Aggregatin suppressed the formation of amyloid plaques in APP transgenic mice, further implying it as an
important factor for Aβ aggregating to form amyloid plaques. These exciting and promising preliminary studies
suggest that a detailed investigation into the potential role of Aggregatin in the formation of amyloid plaques in
AD is warranted. Using a novel transgenic mouse model with conditional ablation of Aggregatin, this study will
not only study whether and how Aggregatin regulates amyloid plaque formation and disease progression, but
also test the feasibility of targeting Aggregatin as a novel therapeutic approach for AD. Amyloid plaque is a
prominent common histopathological feature of in various major neurodegenerative diseases including but not
limited to AD. Our proposed studies of Aggregatin and its connection with amyloid plaque will have very broad
scientific and translational significance.

## Key facts

- **NIH application ID:** 10378210
- **Project number:** 7RF1AG066578-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** MASARU MIYAGI
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,013,931
- **Award type:** 7
- **Project period:** 2020-09-15 → 2022-10-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378210

## Citation

> US National Institutes of Health, RePORTER application 10378210, FAM222A and amyloid plaque deposition in Alzheimer's Disease (7RF1AG066578-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10378210. Licensed CC0.

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