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PMID: 6083566 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 81 ·No. 24 ·1984-12-00 ·Pages 7941-5

Kosik KS, Duffy LK, Dowling MM, Abraham C, McCluskey A, Selkoe DJ

Abstract

Neurofibrillary tangles (NFT) are the principal structural alteration of neuronal cell bodies in Alzheimer disease as well as in normal aging of the human brain. While the ultrastructure of these intraneuronal lesions has been extensively studied, the biochemical composition of the fibers comprising the NFT is unknown. We report the production of three monoclonal antibodies against the microtubule-associated protein 2 (MAP-2), one of which intensely labels Alzheimer NFT. All three antibodies specifically recognize MAP-2 on immunoblots and stain brain tissue in a characteristic dendritic pattern. The three antibodies are directed against at least two different antigenic sites on the MAP-2 molecule, and one appears to recognize a phosphorylation site on MAP-2. That only one of the three antibodies immunolabels NFT suggests that the formation of the tangle involves some modification of the MAP-2 molecule. Our findings suggest that one aspect of Alzheimer-type neurofibrillary pathology is an aggregation of MAP-2 or MAP-2 fragments with altered neurofilamentous elements present in NFT. Normal interactive function, which putatively occurs between neurofilaments and MAP-2, may thus be disrupted in Alzheimer disease.

MeSH Terms
Alzheimer Disease/metabolism,pathology Animals Antibodies, Monoclonal Brain/pathology Brain Chemistry Epitopes/analysis Female Humans Mice Mice, Inbred BALB C Microtubule-Associated Proteins/analysis,immunology Nerve Tissue Proteins/analysis Neurofibrils/ultrastructure Rats
Chemicals
Antibodies, Monoclonal Epitopes Microtubule-Associated Proteins Nerve Tissue Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kosik K S
Duffy L K
Dowling M M
Abraham C
McCluskey A
Selkoe D J
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46 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.81.24.7941
Published
1984-12-00
Pages
7941-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC392269
Subset
IM
Grants
NIA NIH HHS · AG 01397 · United States
NINDS NIH HHS · NS 00835 · United States
NINDS NIH HHS · NS 20110 · United States
External Links
PubMed source DOI: 10.1073/pnas.81.24.7941 PMC Full Text View journal details
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