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

Barbara J. Crain, Weidong Hu, Chun I. Sze, Hilda H. Slunt, Edward H. Koo, Donald L. Price, Gopal Thinakaran, Sangram S. Sisodia

Research output: Contribution to journalArticlepeer-review

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 glycosaminogycan-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 neuronalsprouting or in the aggregation, deposition, and/or persistence of β-amyloid deposits.

Original languageEnglish (US)
Pages (from-to)1087-1095
Number of pages9
JournalAmerican Journal of Pathology
Volume149
Issue number4
StatePublished - Oct 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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