# PAIRED HELICAL FILAMENT AND PLAQUE AMYLOID PROTEINS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1991 · $148,370

## 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, designated the anhydrous,
boiling formic acid (ABFA) technique, has been developed, which completely
solubilizes and denatures the PHFs to make them amenable to chemical
analysis.  A solubilized concentrate of PHFs has been fractionated on
Sepharose-4B and the peak PHF "core" or backbone protein fractions analyzed
by lithium dodecyl sulfate-PAGE (LDS-PAGE).  This gives numerous polymeric
bands and an apparent monomeric molecular weight of 74 kd for the PHF
backbone protein, a value in close agreement to that of the beta protein
gene product, 79 kd.  Electrophoresis in 8 M urea reduces the number of
bands suggesting that they are non-covalent polymers resulting from
hydrophobic interaction:  Amino acid analyses show that the formic acid
method produces modification of only the amino acids, cysteine and cystine.
Initial amino acid sequence analysis revealed the N-terminus of the PHF
backbone protein to be blocked.  This investigation, therefore, will
provide a complete amino acid sequence of the PHF backbone protein by
utilizing chemical and enzymic cleavage to produce overlapping peptides for
amino acid sequence analyses and mass spectroscopy to identify the amino
terminal blocking moiety.  Only methodology that provides acceptable
quantitative yields from starting material will be employed.  The present
data on the composition of the amyloid fibrils composing the "senile"
plaque is conflicting although the beta protein or the beta protein
precursor appears by immunohistochemical studies to be a major component.
An investigation similar to that of the above will therefore, also be
performed on homogeneous preparations of "senile" plaques which are also
solubilized by the ABFA method in order to determine definitively the
molecular weight and amino acid composition and sequence of the amyloid
fibril protein composing them.

## Key facts

- **NIH application ID:** 3121256
- **Project number:** 1R01AG009411-01
- **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:** 1991
- **Award amount:** $148,370
- **Award type:** 1
- **Project period:** 1991-05-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121256

## Citation

> US National Institutes of Health, RePORTER application 3121256, PAIRED HELICAL FILAMENT AND PLAQUE AMYLOID PROTEINS (1R01AG009411-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121256. Licensed CC0.

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