# MOLECULAR CELL BIOLOGY OF AMYLOID PRECURSOR PROTEIN

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1991 · $106,423

## Abstract

The long-range goal of this work concerns molecular mechanisms of cell
death in Alzheimer's disease (AD).  Its immediate focus is to study the
molecular cell biology of amyloid precursor protein (APP).  The
cytoarchitectural nature of APP in situ, its functional role, and the
factors influencing its expression are essentially unknown.  The proposed
aims address these gaps and, additionally, will help to establish a
useful new model for experimental studies of AD neuropathogenesis.
     AIM #1- To characterize the structural biology of APP at cell and
extracellular surfaces, focusing on tests of the hypothesis that APP may
be a cell adhesion molecule.  While the cellular function of APP is
unknown, one major hypothesis based on sequence analysis is that this
protein is a cell adhesion molecule.  To test this hypothesis directly,
and to characterize the structural biology of the APP molecule in situ,
we recently have developed a whole mount EM-immunogold method for
studying APP expression in cultured human nerve cell lines.  Based on our
pilot studies, we propose (1) To verify and extend characterization of
the relationship between APP forms and adhesive microfibrils found at
cell and extracellular surfaces, applying whole mount transmission
electron microscopy-immunogold protocols to SHSY5Y human neuroblastoma
cell cultures. (2) To evaluate the adhesive role of APP, using paradigms
that test adhesion-linked functions such as neurite extension and growth
cone motility (3) To provide initial characterization of a postulated APP
receptor, using isolation protocols based on the adhesive properties of
APP.
          AIM #2- To evaluate the influence of cellular stress factors on
APP expression.  The APP promoter is known to have multiple control
elements, including a stress-related heat shock sequence.  Experiments
therefore have been designed to study APP expression in response to
external influences that can stress nerve cells.  Six factors
incriminated directly or indirectly in the pathogenesis of AD will be
studied (heat shock, Ca++ overload, glucose withdrawal, hypoxia, oxidant
injury, and aluminum).  The distribution of specific APP forms on cell
and culture surfaces will be compared using imaging techniques; the
levels of APP forms associated with cells and culture substratum will be
measured by quantitative immunoblots.  The data will provide essential
tests of the hypothesis that cell stress causes significant changes or
anomalies in APP expression.

## Key facts

- **NIH application ID:** 3121184
- **Project number:** 1R01AG009337-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** EXZVPWZBLUE8
- **Principal Investigator:** WILLIAM L KLEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $106,423
- **Award type:** 1
- **Project period:** 1991-05-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121184

## Citation

> US National Institutes of Health, RePORTER application 3121184, MOLECULAR CELL BIOLOGY OF AMYLOID PRECURSOR PROTEIN (1R01AG009337-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121184. Licensed CC0.

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