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Title: Distribution of precursor amyloid-. beta. -protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques

Abstract

Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid ..beta.. protein. However, the nature of the relationship between NFT and NP and the source of the amyloid ..beta.. proteins found in each have remained unclear. The authors used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-..beta..-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. These findings suggest that the expression of precursor amyloid-..beta..-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, thesemore » results may indicate that the amyloid ..beta.. protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Research Institute of Scripps Clinic, La Jolla, CA (USA)
OSTI Identifier:
6619151
Alternate Identifier(s):
OSTI ID: 6619151
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. U.S.A.; (United States)
Additional Journal Information:
Journal Volume: 85:5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MESSENGER-RNA; TISSUE DISTRIBUTION; NERVOUS SYSTEM DISEASES; PATHOGENESIS; ADULTS; AMINO ACID SEQUENCE; CEREBRUM; HYBRIDIZATION; PATIENTS; PROTEINS; SULFUR 35; AGE GROUPS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; BRAIN; CENTRAL NERVOUS SYSTEM; DAYS LIVING RADIOISOTOPES; DISEASES; DISTRIBUTION; EVEN-ODD NUCLEI; ISOTOPES; LIGHT NUCLEI; MOLECULAR STRUCTURE; NERVOUS SYSTEM; NUCLEI; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; RADIOISOTOPES; RNA; SULFUR ISOTOPES 550201* -- Biochemistry-- Tracer Techniques

Citation Formats

Lewis, D.A., Higgins, G.A., Young, W.G., Goldgaber, D., Gajdusek, D.C., Wilson, M.C., and Morrison, J.H. Distribution of precursor amyloid-. beta. -protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques. United States: N. p., 1988. Web. doi:10.1073/pnas.85.5.1691.
Lewis, D.A., Higgins, G.A., Young, W.G., Goldgaber, D., Gajdusek, D.C., Wilson, M.C., & Morrison, J.H. Distribution of precursor amyloid-. beta. -protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques. United States. doi:10.1073/pnas.85.5.1691.
Lewis, D.A., Higgins, G.A., Young, W.G., Goldgaber, D., Gajdusek, D.C., Wilson, M.C., and Morrison, J.H. Tue . "Distribution of precursor amyloid-. beta. -protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques". United States. doi:10.1073/pnas.85.5.1691.
@article{osti_6619151,
title = {Distribution of precursor amyloid-. beta. -protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques},
author = {Lewis, D.A. and Higgins, G.A. and Young, W.G. and Goldgaber, D. and Gajdusek, D.C. and Wilson, M.C. and Morrison, J.H.},
abstractNote = {Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid ..beta.. protein. However, the nature of the relationship between NFT and NP and the source of the amyloid ..beta.. proteins found in each have remained unclear. The authors used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-..beta..-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. These findings suggest that the expression of precursor amyloid-..beta..-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid ..beta.. protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.},
doi = {10.1073/pnas.85.5.1691},
journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = ,
volume = 85:5,
place = {United States},
year = {1988},
month = {3}
}