title: Selective messenger RNA reduction in Alzheimer's disease.
abstract: The relative abundance of 7 messenger RNAs extracted from Alzheimer and control neocortex were examined by Northern and quantitative dot blot analysis. The average yield of mRNA coding for NF-L, the 68-kDa moiety of neurofilament protein, was reduced to 27% of control when expressed as the percentage of total RNA or 14% when expressed per gram of neocortex. In contrast, the yields of 6 other messenger RNAs fell into two categories: those which were statistically significantly reduced to about 65% of control and those which were not reduced when expressed as percentage of total RNA. The anomalous low abundance of neuron specific NF-L mRNA, coding for the lowest molecular weight moiety of neurofilament proteins, in cerebral cortex of Alzheimer's disease cannot be adequately accounted for by a non-specific effect of brain damage, neuron cell loss or neurons with neurofibrillary degeneration. We speculate that this mRNA decrease is related to a functional deficit of gene expression in Alzheimer's disease, perhaps related to the non-random increase in chromatin compaction previously reported from this laboratory. The inability of neurons to maintain homeostatic amounts of NF-L transcription products may be linked to the accumulation of abnormal filamentous components characteristically associated with the diseased cytoskeleton.
authors.affiliation: Department of Physiology, University of Toronto, Canada.
authors.forename: D R
authors.initials: DR
authors.lastname: McLachlan
authors.forename: W J
authors.initials: WJ
authors.lastname: Lukiw
authors.forename: L
authors.initials: L
authors.lastname: Wong
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.forename: N T
authors.initials: NT
authors.lastname: Bech-Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000032:analysis; D006801:Humans; D007118:Immunoassay; D007381:Intermediate Filament Proteins / Q000032:analysis*; D008875:Middle Aged; D016900:Neurofilament Proteins; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C044882:neurofilament protein L