# PAIRED HELICAL FILAMENTS AND PLAQUE AMYLOID PROTEINS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1993 · $147,740

## Abstract

The paired helical filaments (PHFS) composing the neurofibrillary tangles
have been the subject of chemical investigation for over fifteen years
yet their nature still remains clouded.  A method has been developed,
which  completely  solubilizes  and  denatures  the  PHFs
to  make  them  amenable  to  chemical  analysis.   A  solubilized
concentrate  of  PHFs  has  been  analyzed  on  SDS-PAGE  gels  and
the peak PHF "core" or backbone protein fraction gives an apparent
monomeric molecular weight of 35 kDa.  The major protein eluted from the
SDS gels and bound to a PVDF membrane is found by amino acid sequence
analysis to have a blocked N-terminus.  This protein was then subjected
to tryptic digestion yielding 5 peptide peaks.  A partial amino acid
sequence of the major peptide has been obtained which fails to correspond
to any known protein when compared to a sequence data bank.This
investigation will provide a complete amino acid sequence of the PHF
backbone protein by utilizing further chemical and enzymic cleavage to
produce overlapping peptides for analysis.  The PHF gene will be cloned
based on these sequences.  These studies and the analyses for
polysaccharide and phosphate residues will determine if abnormalities in
post-translational events are responsible for PHF formation.  The amyloid
core of senile plaques has never previously been reproducibly defined.  A
method employing sequentially anhydrous trifluoroacetic acid and 5.8 M
guanidine isothiocyanate solubilizes a concentrate of plaques and
SDS-PAGE reveals a major protein band at 6 kDa.  Amino acid sequence
analysis reveals a blocked N-terminus. This plaque amyloid fibril
protein, which is believed to be composed of the beta protein, will be
subjected to chemical and enzymic digestion in order to define its length
and complete chemical composition.  This analysis should reveal the
cleavage sites of the beta protein precursor leading to the deposition of
the plaque amyloid fibrils and aid in defining its pathogenesis.

## Key facts

- **NIH application ID:** 3121257
- **Project number:** 2R01AG009411-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** GEORGE G GLENNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $147,740
- **Award type:** 2
- **Project period:** 1991-05-01 → 1996-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121257

## Citation

> US National Institutes of Health, RePORTER application 3121257, PAIRED HELICAL FILAMENTS AND PLAQUE AMYLOID PROTEINS (2R01AG009411-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121257. Licensed CC0.

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