Distribution of precursor amyloid-β-protein messenger RNA in human cerebral cortex: Relationship to neurofibrillary tangles and neuritic plaques

D. A. Lewis, G. A. Higgins, W. G. Young, D. Goldgaber, D. C. Gajdusek, M. C. Wilson, John Morrison

Research output: Contribution to journalArticle

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Abstract

Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid β protein. However, the nature of the relationship between NFT and NP and the source of the amyloid β proteins found in each have remained unclear. We used in situ hybridization techniques to map the anatomical distribution of precursor amyloid β-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. In contrast, no correlation was found between the densities of NP and neurons containing precursor amyloid-β-protein mRNA transcripts. These findings suggest that expression of precursor amyloid-β-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 β 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.

Original languageEnglish (US)
Pages (from-to)1691-1695
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number5
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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Neurofibrillary Tangles
Amyloid beta-Protein Precursor
Amyloid Plaques
Cerebral Cortex
Alzheimer Disease
Amyloidogenic Proteins
Messenger RNA
Brain
Neurons
In Situ Hybridization
Peptide Fragments
Neocortex
RNA Precursors
Frontal Lobe
Nervous System Diseases
Proteins

ASJC Scopus subject areas

  • General

Cite this

Distribution of precursor amyloid-β-protein messenger RNA in human cerebral cortex : Relationship to neurofibrillary tangles and neuritic plaques. / Lewis, D. A.; Higgins, G. A.; Young, W. G.; Goldgaber, D.; Gajdusek, D. C.; Wilson, M. C.; Morrison, John.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 5, 01.01.1988, p. 1691-1695.

Research output: Contribution to journalArticle

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