# NEUROFIBRILLARY PATHOLOGY IN ALZHEIMER DISEASE

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1990 · $88,697

## Abstract

The cellular events leading to the pathogenesis of neurofibrillary
pathology (NFP) in Alzheimer's disease (AD) are poorly understood.  This
proposal focuses on the pathogenic mechanisms at the cellular and
subcellular level and focuses on immunoelectron microscopy of the lesions
in well fixed brain tissue, obtained from either biopsy or rapid autopsy.
We propose three studies which will provide significant new insights into
the pathogenesis of NFP.

First, the morphogenesis of abnormal filaments in the dystrophic neurites
characteristic of AD will be studied by the accurate localization of
cytoskeletal proteins in the different types of abnormal and normal
filaments.  In conjunction, studies will establish whether there is
structural continuity between the abnormal filaments and the cytoskeleton.
Further morphometric analysis will be used to determined the organization
of the normal and abnormal filaments and whether neuropil threads
originate from neurofibrillary tangle bearing neurons.

Second, we will determine the chemical association of tubulin and the
neurofilament heavy subunit with paired helical filaments (PHF).
Identification of these proteins in enriched PHF fractions as well as
quantification will be used to establish whether both are chemically
integral PHF components.  In a series of reconstitution experiments using
neurofilament and microtubule proteins we will attempt to understand the
factors responsible for abnormal filament formation in AD based on protein
interaction.

Finally, we will study the aged or alcohol treated rat as a model of NFP.
Immunocytochemistry at the light and electron microscopic levels will be
used to characterize the changes seen in rats and compared to NFP in AD.
These results will serve as the prelude to protein chemical
characterization of NFP in the rat model.

These experiments are expected to provide significant information on a)
the structural role the cytoskeleton plays in NFP formation as well as the
interaction of normal and abnormal structures; b) identification of NFH
and tubulin as components of NFP as well as their importance in abnormal
filament formation; and c) development of a model to study NFP.

## Key facts

- **NIH application ID:** 3121106
- **Project number:** 1R01AG009287-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** GEORGE PERRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $88,697
- **Award type:** 1
- **Project period:** 1990-09-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121106

## Citation

> US National Institutes of Health, RePORTER application 3121106, NEUROFIBRILLARY PATHOLOGY IN ALZHEIMER DISEASE (1R01AG009287-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121106. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*