title: Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer's disease.
abstract: Cholinesterase inhibitors (ChEIs) are widely used for the symptomatic treatment of Alzheimer's disease (AD). In vitro and in animal studies, ChEIs have been shown to influence the processing of Abeta and the phosphorylation of tau, proteins that are the principal constituents of the plaques and neurofibrillary tangles, respectively, in AD brain. However, little is known about the effects of these drugs on Abeta and tau pathology in AD. Using avidin-biotin immunohistochemistry and computer-assisted image analysis, we compared Abeta and tau loads in the frontal and temporal cortices of 72 brains from matched cohorts of AD patients who had or had not received ChEIs. Patients treated with ChEIs had accumulated significantly more phospho-tau in their cerebral cortex than had untreated patients (P = 0.004). Abeta accumulation was reduced but not significantly. These data raise the possibility that increased tau phosphorylation may influence long-term clinical responsiveness to ChEIs.
authors.affiliation: Dementia Research Group, Department of Clinical Science at North Bristol, University of Bristol, Bristol, UK. katy.chalmers@bristol.ac.uk
authors.forename: Katy A
authors.initials: KA
authors.lastname: Chalmers
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Perry
authors.forename: Robert
authors.initials: R
authors.lastname: Perry
authors.forename: Clive G
authors.initials: CG
authors.lastname: Ballard
authors.forename: Seth
authors.initials: S
authors.lastname: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D013995:Time; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D016875:tau Proteins