# ABNORMAL FIBROUS ASSEMBLIES OF ALZHEIMER'S DISEASE

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1990 · $87,507

## Abstract

The molecular organization of paired helical filaments, amyloid plaque
cores, and cerebrovascular amyloid isolated from Alzheimer's disease (AD)
brain will be studied using X-ray diffraction and electron microscopy.
High-resolution X=ray patterns will be obtained from isolates of the
abnormal fibrous assemblies for comparison with patterns from in vitro
assemblies of synthetic polypeptides having sequence homologies with the AD
amyloid beta-protein.

To obtain patterns that are suitable for such comparisons, the assemblies
will be oriented by exposure of pellets or concentrated solutions to an
external magnetic field of 2 Tesla.  The magnetically-induced orientation
of similar filamentous structures (as diverse as filamentous bacteriophage,
whole retinal rods, nucleic acids, and sickle cell hemoglobin fibers) has
been previously shown to substantially enhance the quality of the
diffraction data.  The X-ray scatter from our various fibrous assemblies
will also be enhanced by altering the electron density of the bathing
medium, using negative stains, and labeling reactive amino acid residues
with heavy metals.  Appropriately contrasted and well-oriented pellets will
allow the detection of weak scatter that arises from the packing of the
structural units within and along the fibres.  Accurate determination of
the spacings and of the integral widths of the X-ray reflections will
provide a measure of the sizes of the diffracting regions and the lengths
of the polypeptide chains constituting the structure.

Determining the dimensions and spatial organization of the structural units
that comprise paired helical filaments, AD amyloids and in vitro assemblies
will illuminate our understanding of their formation, interrelationships,
and stability, and will provide insight on how they might be related to or
derive from normally occurring cytoskeletal components in the neuron.  Of
more general interest, our findings will also be relevant to the systemic
amyloidoses, and to the problem of protein folding.

## Key facts

- **NIH application ID:** 3120290
- **Project number:** 5R01AG008572-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** DANIEL A KIRSCHNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $87,507
- **Award type:** 5
- **Project period:** 1989-08-02 → 1992-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120290

## Citation

> US National Institutes of Health, RePORTER application 3120290, ABNORMAL FIBROUS ASSEMBLIES OF ALZHEIMER'S DISEASE (5R01AG008572-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120290. Licensed CC0.

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