# BIOLOGY OF ALZHEIMER PAIRED HELICAL FILAMENTS

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1992 · $154,095

## Abstract

Alzheimer's disease (AD) is characterized by the accumulation of
neurofibrillary tangles (NFTs), senile plaques (SPs) and neuropil threads
(NTs) in selected telencephalic regions that are especially vulnerable to
degeneration.  Previous studies have identified a common structural
elements in NFTs, NTs and the dystrophic neurites around SPs that are
referred to as paired-helical filaments (PHFs).  Recently, we showed that a
form of SDS-soluble PHFs are composed of A68, a group of putative AD
specific proteins.  Further, we showed that A68 proteins are abnormally
phosphorylated variants of tau, a group of low molecular weight microtubule
associated proteins, and that the single KSPV in tau is a phosphate
acceptor site in A68 but not in normal human tau.

This proposal describes timely experiments to determine how normal tau is
transformed into A68, assembled into PHFs and subsequently incorporated
into AD NFTs.  Specifically, we will determine the extent to which A68 and
tau are identical at the amino acid levels in order to exclude the
possibility that the primary structure of A68 differs from that of tau.  We
will elucidate the exact sites of abnormal phosphorylation in A68 that
distinguish it from normal tau.  We will also define conditions for the in
vitro reassembly of highly purified soluble A68 into PHFs.  Finally, we
will assess whether or not NFT-like structures can be formed by the
interaction of A68 PHFs with other suspected protein components of NFTs
under defined conditions in vitro.  The successful completion of these
studies will lead to the complete characterization of A68, the major
subunit of PHFs, and they will provide new insight into how PHFs and NFTs
are formed from A68 alone or in concert with other neuronal proteins.

## Key facts

- **NIH application ID:** 3122168
- **Project number:** 1R01AG010210-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** VIRGINIA M LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $154,095
- **Award type:** 1
- **Project period:** 1992-06-15 → 1997-05-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122168

## Citation

> US National Institutes of Health, RePORTER application 3122168, BIOLOGY OF ALZHEIMER PAIRED HELICAL FILAMENTS (1R01AG010210-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122168. Licensed CC0.

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