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Sequence of a human MAP-2 region sharing epitopes with Alzheimer neurofibrillary tangles

M Dammerman1, S H Yen, B Shafit-Zagardo

  • 1Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.

Journal of Neuroscience Research
|December 1, 1989
PubMed

Insights

Microtubule-associated protein 2 (MAP-2) contains Alzheimer's neurofibrillary tangle (NFT) epitopes. These epitopes are integral to NFT structure, located on the MAP-2 projection arm.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Microtubule-associated protein 2 (MAP-2) is a key neuronal protein.
  • MAP-2 shares epitopes with Alzheimer's neurofibrillary tangles (NFTs).
  • The role of MAP-2 in NFT formation remains unclear due to antibody staining issues.

Purpose of the Study:

  • To identify and localize the specific epitopes of MAP-2 within neurofibrillary tangles (NFTs).
  • To clarify the integral role of MAP-2 in the composition of NFTs.

Main Methods:

  • Sequencing of a partial MAP-2 cDNA (1.7 kb) encoding NFT epitopes.
  • Detergent extraction of NFT preparations to assess epitope stability.
  • Expression vector analysis using cDNA restriction fragments to map epitopes.

Main Results:

  • A 1.7 kb MAP-2 cDNA fragment encoding at least three NFT epitopes was sequenced.
  • These epitopes were resistant to detergent extraction, indicating they are integral to NFTs.
  • Epitopes were localized to a 51-amino-acid region on the MAP-2 projection arm, distal to the microtubule-binding domain.

Conclusions:

  • MAP-2 contains integral components of neurofibrillary tangles (NFTs).
  • The identified MAP-2 epitopes are crucial for NFT structure.
  • This finding clarifies the role of MAP-2 in the pathogenesis of Alzheimer's disease.

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