# MAP 5, SPROUTING, AND ALZHEIMER'S DISEASE PATHOLOGY

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 1992 · $123,778

## Abstract

The long term objectives of this proposal are to examine the mechanisms
underlie the cytoskeletal alterations associated with Alzheimer's disease
(AD) neuropathology.  Specifically, we propose to examine i) the ability
that sprouting contributes to the cytoskeletal alterations characteristic
of AD, and ii) the association of a fetal or 'early' microtubule-associated
protein, MAP5, with AD pathology.  We hypothesize that there is a fine
balance between plasticity and pathology and that sprouting-related
alterations may be an early event in the development of AD pathology.

The specific questions which this proposal aims to answer include: 1) Is
MAP5 present in neurofibrillary tangles, neuritic plaques, or neuropil
threads and is MAP5 a component of paired helical filaments? 2) Does the
shift in the cellular compartmentation of MAP5 in AD represent an early
event in the development of pathology? 3) Are the immunocytochemical
alterations accompanied by corresponding changes in mRNA expression? 4) Do
similar alterations in protein and mRNA expression occur in the rat brain
in association with lesion-induced sprouting? 5) Do components of the
neuritic plaque, such as Beta-amyloid and basic FGF, influence the
immunoreactivity or phosphorylation of MAP5, tau, and early tubulin
isotypes, or alter the expression of their encoding mRNAs?

Aims 1-3 will be examined in human brain tissues, obtained at autopsy, from
individuals with a clinical diagnosis of 'probable AD' and from
neurologically normal controls.  Many of these individuals will have been
clinically evaluated at the Sanders-Brown Center on Aging.  Aim 4 will
examine rats in which either the entorhinal cortex or fimbria-fornix has
been lesioned.  Aim 5 will utilize cultured rat hippocampal neurons and
represents a collaboration with Dr. Mark Mattson.  A variety of
experimental methodologies will be used. These include immunocytochemistry,
Western blots, in situ hybridization, ribonuclease protection assay,
subcellular fractionation, preparation of PHF-enriched fractions, and
confocal and immunoelectron microscopy.  The immunocytochemistry
experiments will employ a panel of antibodies against MAP5. Where possible,
the various probes and methods will be used on tissues obtained from the
same individual to allow comparison of the results.

Results obtained from these experiments will enable us to compare
sprouting-related alterations in cytoskeletal proteins with the alterations
observed in AD.  This is essential for evaluation of the possible role of
sprouting in the pathogenesis of Alzheimer's disease.

## Key facts

- **NIH application ID:** 3122620
- **Project number:** 5R01AG010678-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **SAM.gov UEI:** H1HYA8Z1NTM5
- **Principal Investigator:** James W. Geddes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $123,778
- **Award type:** 5
- **Project period:** 1991-09-29 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122620

## Citation

> US National Institutes of Health, RePORTER application 3122620, MAP 5, SPROUTING, AND ALZHEIMER'S DISEASE PATHOLOGY (5R01AG010678-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122620. Licensed CC0.

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