# AMYLOID PRECURSOR IN ALZHEIMER'S DISEASE BRAIN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1993 · $69,861

## Abstract

Alzheimer's disease (AD) is characterized by extracellular deposits of
beta-protein derived from an amyloid precursor protein (APP) which when
mutated at APP717 appears to result in AD.  Along with other
investigators, we have found two pathways for amyloid precursor
degradation, secretion and lysosomal degradation.  The lysosomal
degradative pathway normally removes potentially amyloidogenic and other
C-terminal APP fragments from cultured cells suggesting that a deficiency
in this pathway in aging or Alzheimer's disease could promote
beta-protein deposition.  However, no differences between normal and AD
in beta-containing, full-length APP or C-terminal fragments have been
found, while there is a suggestion of age changes.  APP metabolism is
modified by protein kinase C (PK-C) and we have shown altered PK-C in AD.
We propose to reexamine the relationship of aging and AD to PK-C and to
APP and its metabolites to determine whether age or AD-linked changes
actually occur.  We have preliminary evidence that specific, age-related,
factors can modulate the rate of C-terminal APP degradation, and
possibly, secretion-cleavage sites.  We propose to test whether these and
related factors can modulate the expression of potentially amyloidogenic
fragments in cell culture, in particular, in the endosomal lysosomal
pathway as suggested by our preliminary data.  We propose to examine APP
metabolism in a panel of cells transfected to overproduce these factors
and to make a related series of neuronal cells.  We have demonstrated
beta protein toxicity in culture and identified agents which can block
this toxicity.  We propose to examine these phenomena in relation to APP.
These experiments should help identify agents which normally modulate the
rate of amyloid production and, appear to offer new directions for
treatment and prevention of AD.

## Key facts

- **NIH application ID:** 3120820
- **Project number:** 2R01AG009009-04
- **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:** 1993
- **Award amount:** $69,861
- **Award type:** 2
- **Project period:** 1990-05-02 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120820

## Citation

> US National Institutes of Health, RePORTER application 3120820, AMYLOID PRECURSOR IN ALZHEIMER'S DISEASE BRAIN (2R01AG009009-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120820. Licensed CC0.

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