Open AccessAltered levels of amyloid protein precursor transcripts in the basal forebrain of behaviorally impaired aged rats.
Author(s) -
Gerald A. Higgins,
George A. Oyler,
Rachael L. Neve,
Karen S. Chen,
Fred H. Gage
Publication year - 1990
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.87.8.3032
Subject(s) - basal forebrain , forebrain , in situ hybridization , amyloid precursor protein , endocrinology , neurochemical , biology , medicine , basal (medicine) , cholinergic neuron , alzheimer's disease , neuroscience , messenger rna , central nervous system , disease , biochemistry , gene , insulin
The beta/A4 protein is a constituent of plaque and vascular amyloid deposits in Alzheimer disease. Previous studies have shown increased levels of amyloid protein precursor (APP) mRNA in basal forebrain neurons in the disease. Morphological and neurochemical changes occur within the forebrain in Alzheimer disease and are also correlated with behavioral impairments in aged rats. Recent studies suggest that decreased nerve growth factor responsiveness of basal forebrain neurons is a feature of normal aging and of Alzheimer disease. We have used in situ hybridization to show that the abundance of specific forms of APP mRNA, which contain an inserted Kunitz-type serine protease inhibitor motif (APP-751, APP-770, and APP-related 563), are increased relative to the noninserted form (APP-695) of APP mRNA in the basal forebrain of aged rats. This increase appears to be specific to animals who exhibit spatial memory deficits but not aged rats without behavioral impairments.