# TAU STRUCTURES IN ALZHEIMER'S TANGLES AND MICROTUBULES

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1993 · $196,975

## Abstract

Our long term objective is to understand the pathogenesis of Alzheimer
disease (AD).  Our short term objective is to understand the mechanism
of neurofibrillary degeneration in AD brain.  We propose to definitively
identify by gold-immuno-labeling the approximate 2.1nm diameter filaments
that have been found in Alzheimer neurofibrillary tangles (NFT) isolated
in the absence of detergent.  These approximate 2.1 nm filaments have the
same structure as the approximate 2.1.nm bovine tau polymer filaments
which are triple-stranded and left-hand helical.  Isolated whole NFT will
be labeled in separate preparations with gold-conjugated-antibodies to
tau, ubiquitin, and amyloid-Beta-protein.  The structure of the NFT and
the localization of the immuno-gold labels will be investigated in whole
NFT that have been freeze-dried on a millipore filter and vertically
platinum-carbon (Pt-C) replicated.  We also propose to investigate how
the tau monomers (about 1.0nm diam. by about 63 nm long) are aligned with
one another within the three stranded tau polymer.  We will study the tau
polymers structure by binding antibody fragments, Fab' or F(ab)'2, to the
N or C-terminal region and to the microtubule binding domain first in
separate spreading experiments and then in a double immuno-labelling
experiment.  We propose to investigate whether the tau polymer or the
monomer configuration is active in stabilizing long microtubules by
direct visualization of the microtubule surfaces in vertically Pt-C
replicated freeze-dried preparations.  Finally we propose to correlate
tau's inverse temperature transition at 197 nm in the circular dichroism
(CD) spectrum with tau's length at the inverse temperature transition
(about 30 degrees C), as well as above (about 37 degrees C) and below
this temperature(4-10 degrees C.  Since the tau polymers are of different
lengths, immuno-labelled periodic intervals will be measured as a
function of temperature.  Since the inverse temperature transition at 197
nm in the CD spectrum appears to correlate with tau's ability to
stimulate tubulin polymerization above 30 degrees C and not below 20
degrees C, its important that tau's length be correlated with this
temperature effect.  The work on tau polymer, is very relevant to
Alzheimers disease, since normal tau's structure and function have to
first be understood to assess how pathological abnormally phosphorylated
tau in NFT differs from it.

## Key facts

- **NIH application ID:** 3123043
- **Project number:** 1R01AG011054-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** GEORGE C RUBEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $196,975
- **Award type:** 1
- **Project period:** 1993-03-01 → 1996-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123043

## Citation

> US National Institutes of Health, RePORTER application 3123043, TAU STRUCTURES IN ALZHEIMER'S TANGLES AND MICROTUBULES (1R01AG011054-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123043. Licensed CC0.

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