title: beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects.
abstract: Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.
authors.affiliation: Miriam Marks Department of Neurochemistry, Institute of Neurology, London, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Procter
authors.forename: P T
authors.initials: PT
authors.lastname: Francis
authors.forename: C
authors.initials: C
authors.lastname: Holmes
authors.forename: M T
authors.initials: MT
authors.lastname: Webster
authors.forename: M
authors.initials: M
authors.lastname: Qume
authors.forename: G C
authors.initials: GC
authors.lastname: Stratmann
authors.forename: R
authors.initials: R
authors.lastname: Doshi
authors.forename: D M
authors.initials: DM
authors.lastname: Mann
authors.forename: P J
authors.initials: PJ
authors.lastname: Harrison
authors.forename: R C
authors.initials: RC
authors.lastname: Pearson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger