# HEPARIN-BINDING GROWTH FACTORS IN AGING & ALZHEIMER'S

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 1993 · $83,066

## Abstract

A fundamental question remains unresolved regarding the significance of the
increased levels of basic Fibroblast Growth Factor (bFGF) which we have
observed in Alzheimer's disease.  Is this increase an active process that
enhances Beta/A4 amyloid deposition and occurs as a function of age-related
growth factor dysregulation; or is this increase a passive process which
results from the intrinsic tendency of bFGF and possibly the other newly
identified heparin-binding growth factors, to bind to the heparan-sulfate
proteoglycans recently shown to be associated with Beta/A4 amyloid
deposition?

The proposed studies will use a carefully planned comprehensive post-mortem
study of control and Alzheimer brains to test the following hypotheses: 1)
Abnormalities in heparin-binding growth factors correlate with the severity
of Alzheimer's disease pathology; 2) Heparin-binding growth factors are
altered early in the course of disease and precede the appearance of
Beta/A4 amyloid-containing senile plaques; 3) Heparin-binding growth
factors increase as a function of the normal aging process.

Biochemical and morphologic analyses of tissues obtained from the same
brain regions will be performed in order to compare the findings in five
representative brain regions severely affected by Alzheimer's disease with
five representative regions that are typically spared by the disease
process.  The proposed studies will include: a) qualitative
immunocytochemical analyses of basic fibroblast growth factor (bFGF),
acidic fibroblast growth factor  (aFGF), vascular endothelial growth factor
(VEGF) and heparin binding neurotrophic factor (HBNF); b) qualitative
analyses of the distribution of bFGF, aFGF, VEGF and HBNF mRNA
hybridization signal density; c) quantitative protein assays for bFGF,
aFGF, VEGF and HBNF (RIA and Western analyses); and d) morphometric
analyses of senile plaque, neurofibrillary tangle and reactive astrocyte
counts/mm2.  The morphologic and biochemical alterations observed in 20
patients with early Alzheimer's disease will be compared to 20 patient with
advanced Alzheimer's disease, as well as to their respective age, sex, and
post-mortem interval matched controls.  In addition, we will examine
possible heparin binding growth factor abnormalities which may occur as a
function of the normal aging process by assessing these same parameters in
patients who expire during the 3rd, 6th and 9th decades.

Current evidence suggests that basic fibroblast growth factor may be an
important neurotrophic factor in the adult central nervous system.  The
data obtained from these studies will provide new insights that are
essential in designing heparin-binding growth factor treatment strategies
for Alzheimer's disease.  An active relationship to Beta/A4 amyloid
deposition would suggest a need for the utilization of heparin-binding
growth factor antagonists.  Alternatively, a passive relationship to
Beta/A4 amyloid deposition would necessitate the use of heparin-binding
...

## Key facts

- **NIH application ID:** 3122631
- **Project number:** 7R01AG010682-03
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **SAM.gov UEI:** N876TLXYGCG4
- **Principal Investigator:** EDWARD G STOPA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $83,066
- **Award type:** 7
- **Project period:** 1991-09-29 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122631

## Citation

> US National Institutes of Health, RePORTER application 3122631, HEPARIN-BINDING GROWTH FACTORS IN AGING & ALZHEIMER'S (7R01AG010682-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122631. Licensed CC0.

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