# REGULATION OF ALZHEIMER AMYLOID PRECURSOR GENE

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 1990 · $142,023

## Abstract

The extracellular deposition of amyloid B protein in cores of neuritic
plaques and walls of blood vessels in brains and leptomeninges is a
neuropathological hallmark of aging, Alzheimers disease (AD), Down
syndrome, and hereditary cerebral hemorrhage with amyloidosis (Dutch type).
The identification of the amyloid beta protein precursor (APP) gene, its
localization to human chromosome 21, and its expression in various tissues
and cell types presents an opportunity to determine the pathological
process leading to the formation of amyloid beta protein. The APP gene has
a complex transcriptional unit with two polyadenylation sites. It encodes
multiple transcripts for a family of secreted proteins. One of these
proteins is protease nexin II, which inhibits certain serine proteases. The
APP gene is differentially expressed in all major tissues. In brain it is
expressed primarily, but not exclusively, in neurons. The apparent
overexpression of the APP gene in Down syndrome and in certain areas of the
brain of AD patients indicates a possibility that this overexpression might
be a critical requirement for AD neuropathology and is probably an
indicator of a much broader abnormality in gene regulation for the disease.

The goals of this project are designed to study regulatory mechanisms of
transcription responsible for the control of the APP gene expression and to
identify factors that are responsible for abnormal regulation of the APP
gene expression in aging and in Alzheimers disease. We will use recombinant
DNA clones and DNA sequence information already available to identify
regulatory sequences in the APP promoter, and to discover putative
regulatory factors that bind to the promoter of the APP gene. To accomplish
this, we propose to locate the major block of regulatory elements of the
APP gene and to establish its 5' and 3' boundaries. We will demonstrate
that these sequences are sufficient to specify the APP gene expression in
different cell types by investigating the expression of hybrid genes
containing these regulatory elements linked to simple reporter genes. We
will identify component sequence motifs within the promoter that are
important for differential expression of the APP gene. Next, we will
identify nuclear factors that bind to these regulatory elements. We will
als identify factors, or mediators, that can modulate the expression of the
APP gene. APP gene products ar essential for cell growth and at least one
of these product, protease nexin II, inhibits epidermal growth factor
binding protein and gamma subunit of nerve growth factor. The major focus
of this part of the project will be on the ability of different factors to
modulate the expression of the APP gene. The expression of these modulators
of the APP gene in aged human brain and in Alzheimers disease will help in
the understanding of both the aging process and the disease.

## Key facts

- **NIH application ID:** 3121162
- **Project number:** 1R01AG009320-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **SAM.gov UEI:** M746VC6XMNH9
- **Principal Investigator:** DMITRY Y GOLDGABER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $142,023
- **Award type:** 1
- **Project period:** 1990-09-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121162

## Citation

> US National Institutes of Health, RePORTER application 3121162, REGULATION OF ALZHEIMER AMYLOID PRECURSOR GENE (1R01AG009320-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121162. Licensed CC0.

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