# EXPRESSION STUDIES ON ALZHIEMER'S DISEASE RELATED GENES

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1991 · $108,769

## Abstract

The overall goal of this project is to understand how the expression of
proteins important in Alzheimer's disease is controlled in the brain and
how that control is altered in the disease state.

The identification of the two protein components (alpha-1-antichymotrypsin
and the Beta-protein) of the neuropathological amyloid deposits in
Alzheimer's disease (AD) brain has opened the way of how these molecules
come to be expressed.  We have found that alpha-1-antichymotrypsin (ACT) is
over expressed in those regions of Alzheimer brain affected by the disease,
specifically in astrocytes.  There are also differences between Alzheimer's
disease patients and controls in the levels of the different beta-protein
precursor mRNAs, and beta-protein precursor can be shown to be over-
expressed in astrocytes in models of brain damage.  A protease, Clipsin,
that we have purified, is a strong candidate for a cleavage enzyme that can
release the beta-protein from its precursor, and is also expressed in
brain, probably in mast cells.  Thus changes in the expression of two and
possibly three proteins characterize AD and may underlie the mechanism of
the disease.

We wish to discover how the changes in gene expression observed in AD come
about and whether they are a direct result of mutation.  (25-50 percent of
AD cases arise in certain families and appear to be inherited as an
autosomal dominant trait.)  Specifically, we propose a series of
experiments designed to determine (1) the signaling molecules responsible
for inducing ACT, beta-protein precursor, and potentially Clipsin
expression in cultured cells-astrocytes and mast cells, (2) the DNA
sequences in the regulatory region of these genes which respond to the
inducing signals, (3) whether over-expression of ACT in transgenic mice can
mimic the over-expression in AD and lead to neuropathology, and (4)
whether, and how, the gene coding ACT may be mutant in AD, resulting in
aberrant expression.

## Key facts

- **NIH application ID:** 3121578
- **Project number:** 2R01AG009665-06A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** Huntington Potter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $108,769
- **Award type:** 2
- **Project period:** 1991-01-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121578

## Citation

> US National Institutes of Health, RePORTER application 3121578, EXPRESSION STUDIES ON ALZHIEMER'S DISEASE RELATED GENES (2R01AG009665-06A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121578. Licensed CC0.

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