# EXPRESSION AND PROCESSING OF APP VARIANTS

> **NIH NIH R01** · NEW YORK UNIVERSITY · 1993 · $208,774

## Abstract

The histopathology characterizing Alzheimer's disease (AD) involves
deposition of amyloid protein (Abeta) in brain parenchyma and cerebral
vessel walls, and intraneuronal neurofibrillary tangles.  In patients with
hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D),
alpha beta is deposited predominantly in the brain vasculature, causing
strokes and early death.  Alphabeta is an aberrant degradation product of
an amyloid precursor protein (APP), encoded by a single gene on chromosome
21).  To date, mutations in the APP gene have been found only in HCHWA-D
and in a few families with familial AD (FAD) of early age of onset.  The
mutations segregate with the disease, indicating a possible role in
amyloidogenesis.

HCHWA-D and FAD are good models to examine the common features of diseases
involving alphabeta deposition.  These features include the mechanisms of
APP processing, tissue origin of the alphabeta, and the APP form or a
fragment thereof that is the source of alphabeta.  These systems can also
be used to study the causes of the clinico-pathological differences between
AD, FAD and HCHWA-D.

We propose:  1:  to study the APP gene expression in HCHWA-D patients -
that is, to identify the mRNA forms expressed; to determine which of the
APP MRNA forms harbor the mutation; and to determine the tissue
distribution of the mutated and normal alleles.  2: to establish in vitro
models by immortalizing cells originating from HCHWA-D patients.  These
cells endogenously express the mutated APP gene and may contain aberrant
factor(s) yet unknown, specific to the disease.  The effect of mutations
found in HCHWA-D and FAP patients on APP processing will also be tested in
transiently or permanently transfected tissue culture cell lines of
different origin.  3;  to develop an animal model by constructing
transgenic mice, in order to test whether the mutations in the APP gene
cause accelerated alphabeta deposition in the brain.  The model may
contribute to our understanding of the factors involved in the rate and
site of amyloid deposition.  4:  to study the contribution of specific
sequences of the APP gene to prevention versus acceleration of amyloid
fibril formation by analysis of the in vitro and in vivo expression of the
APP gene following site-specific mutagenesis.

## Key facts

- **NIH application ID:** 3123407
- **Project number:** 5R01AG011481-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **SAM.gov UEI:** NX9PXMKW5KW8
- **Principal Investigator:** EFRAT LEVY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $208,774
- **Award type:** 5
- **Project period:** 1992-09-30 → 1995-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123407

## Citation

> US National Institutes of Health, RePORTER application 3123407, EXPRESSION AND PROCESSING OF APP VARIANTS (5R01AG011481-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123407. Licensed CC0.

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