# ABCA7 dysfunction in Alzheimer's disease pathogenesis

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2021 · $435,750

## Abstract

Project Summary
Alzheimer’s disease (AD) represents one of the foremost healthcare challenges of our times and is a leading
cause of death worldwide. AD accounts for the overwhelming majority of dementias, which affect over 35 million
people worldwide. This number is expected to double every twenty years. Dysfunction of the Adenosine
triphosphate (ATP) Binding Cassette Subfamily A member 7 (ABCA7) transporter has been linked to both early
and late onset AD through alterations in lipid homeostasis, Amyloid-Beta (Aβ) homeostasis, and phagocytosis.
ABCA7 single nucleotide polymorphisms have been associated with late onset AD, suggesting that targeting
ABCA7 could pave the way forward for new therapeutic AD strategies. The long-term objectives of this project
are to gain mechanistic insight into human ABCA7 (hABCA7). We will use a combination of high-resolution
structural analysis, in vitro functional characterization, and discovery of antibody and small molecule binders for
hABCA7. The latter will aid in diagnostics and targeting, or function as potentiators and/or correctors of hABCA7
dysfunction. Specific Aim 1 deals the functional characterization of ABCA7 ATPase activity and the
establishment of an in vitro transport assay to assay the lipid specificities and transport properties of the
transporter and probe its interaction with different apolipoproteins. Specific Aim 2 deals with the detailed cryo-
EM analysis of hABCA7 alone and in combination with nucleotides, different lipid environments, and small
molecule and antibody based binders. Our results will shed light on the physiological functioning of human
ABCA7, which is as of yet poorly understood, and validate its potential utilization as a therapeutic target for which
future antibody and drug discovery efforts can be directed, thereby bridging basic and translational research for
this relatively unexplored area of AD research.

## Key facts

- **NIH application ID:** 10212863
- **Project number:** 1R21AG069180-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Amer Alam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $435,750
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212863

## Citation

> US National Institutes of Health, RePORTER application 10212863, ABCA7 dysfunction in Alzheimer's disease pathogenesis (1R21AG069180-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212863. Licensed CC0.

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