# METABOLISM OF ALZHEIMER AMYLOID B-PROTEIN PRECURSOR

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1991 · $117,159

## Abstract

Aberrant amyloid beta-protein precursor (ABPP) metabolism is probably a
major early event in Alzheimer's disease (AD) pathogenesis leading to
amyloid plaques.  We and others have identified two major pathways for ABPP
metabolism, viz. secretion and lysosomal degradation.  Secretion involves
cleavage from the membrane form to release a soluble, shorter N-terminal
ABPP and a small membrane C-terminal reactive form.  We do not yet know
where normal cleavage is in relation to the beta-protein region, nor what
processes are involved in regulating secretion v.s. putative lysosomal
degradation.  We have recently discovered that ABPP is regulated by
fibroblast basic growth factor (FGF) and that FGF is elevated in AD brain
and abnormally distributed in and around plaques suggesting a possible role
in putative plaque-associated abnormalities in ABPP.  We have recently
reported preliminary evidence for reduced ABPP mRNA and ABPP release in
cultured familial Alzheimer disease fibroblasts.  Although the ABPP gene
and a familial Alzheimer's disease (FAD) gene are both located on
chromosome 21, it is not known whether the FAD gene modulates ABPP mRNA
expression or ABPP metabolism.  The proposed studies are designed to
investigate these problems in genetically engineered human neuronal and
fibroblast cell lines and in AD and control fibroblasts.

## Key facts

- **NIH application ID:** 3120821
- **Project number:** 5R01AG009009-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** GREGORY M COLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $117,159
- **Award type:** 5
- **Project period:** 1990-05-02 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120821

## Citation

> US National Institutes of Health, RePORTER application 3120821, METABOLISM OF ALZHEIMER AMYLOID B-PROTEIN PRECURSOR (5R01AG009009-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120821. Licensed CC0.

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