title: The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease.
abstract: Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.
authors.affiliation: Sun Health Research Institute, Sun City, Arizona 85351, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Beach
authors.forename: Y M
authors.initials: YM
authors.lastname: Kuo
authors.forename: K
authors.initials: K
authors.lastname: Spiegel
authors.forename: M R
authors.initials: MR
authors.lastname: Emmerling
authors.forename: L I
authors.initials: LI
authors.lastname: Sue
authors.forename: K
authors.initials: K
authors.lastname: Kokjohn
authors.forename: A E
authors.initials: AE
authors.lastname: Roher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D002795:Choline O-Acetyltransferase / Q000172:deficiency* / Q000378:metabolism; D018450:Disease Progression; D005625:Frontal Lobe / Q000201:enzymology / Q000473:pathology; D006179:Gyrus Cinguli / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000473:pathology; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000201:enzymology / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D002795:Choline O-Acetyltransferase