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Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.

Abstract
Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits.
AuthorsB J Crain, W Hu, C I Sze, H H Slunt, E H Koo, D L Price, G Thinakaran, S S Sisodia
JournalThe American journal of pathology (Am J Pathol) Vol. 149 Issue 4 Pg. 1087-95 (Oct 1996) ISSN: 0002-9440 [Print] United States
PMID8863657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amyloid beta-Protein Precursor
  • RNA, Messenger
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (metabolism)
  • Amyloid beta-Protein Precursor (analysis, metabolism)
  • Brain (embryology, metabolism)
  • Brain Chemistry
  • Humans
  • Middle Aged
  • RNA, Messenger (metabolism)

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