# DEGENERATION--EPINEPHRINE NEURONS IN ALZHEIMER'S DISEASE

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 1992 · $57,514

## Abstract

The long term aims of this project are 1) to determine whether 3,4
dihydroxy-pheylglycolaldehyde (DOPEGAL) is an endogenous neurotoxin; 2) to
determine whether in Alzheimer's disease (AD) the concentration of DOPEGAL
increases in epinephrine (Epi) nerve cell bodies where it has access to DNA
and where binding to DNA could decrease transcription of the mRNAs of
functionally important proteins.  Four experiments are proposed:  1. The
concentration of DOPEGAL and enzymes involved in its synthesis will be
measured in Epi neuronal cell bodies in AD and controls using gas
chromatography-mass spectrometry and radiochemical assays.  2. The mRNA
levels of catecholamine synthesizing enzymes will be measured in Epi
neuronal cell bodies in AD and controls using polymerase chain reaction
(PCR) and quantitative autoradiography.  3. In vivo toxicity will be
determined by injecting DOPEGAL onto norepinephrine neurons in the rat
locus ceruleus.  Histologic evidence of toxicity will be determined by
counting neurons and measuring cross sectional areas of neurons identified
immunohistochemically.  Chemical evidence of toxicity will be determined by
measuring activity and amounts of catecholamine (CA) synthesizing enzymes
using radiochemical and immunochemical assays, CA enzyme mRNA levels will
be measured using polymerase chain reaction with autoradiography and
quantitative densitometry.  4. The precise identity of the neurotoxin and
whether its effects are mediated by extracellular cell surface receptor
mechanisms or by purely intracellular mechanisms of toxicity will be
determined in vitro using cultured adrenal medullary explants.  Evidence of
toxicity will be determined using the above histological and chemical
procedures.  In addition, HPLC-EC measurements of the MAO-A metabolites
will be made to determine their uptake into cells.  CA uptake blockers will
be used to determine if effects are mediated by intracellular mechanisms.

Neuronal death is the anatomic basis for clinical symptoms in AD yet
cellular and subcellular mechanisms underlying neuronal degeneration are
poorly understood.  The Epi neurotransmitter system is affected late in AD.
While Epi neurons are undergoing degeneration there is no cell loss making
it an ideal system to look at the biochemical mechanisms of neuronal
degeneration.

## Key facts

- **NIH application ID:** 3120947
- **Project number:** 5R01AG009188-02
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **SAM.gov UEI:** JNBLLTBTLLD8
- **Principal Investigator:** WILLIAM J BURKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $57,514
- **Award type:** 5
- **Project period:** 1991-06-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120947

## Citation

> US National Institutes of Health, RePORTER application 3120947, DEGENERATION--EPINEPHRINE NEURONS IN ALZHEIMER'S DISEASE (5R01AG009188-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120947. Licensed CC0.

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