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 Aβ 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 Aβ and tau pathology in AD. Using avidin-biotin immunohistochemistry and computer-assisted image analysis, we compared Aβ 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). Aβ accumulation was reduced but not significantly. These data raise the possibility that increased tau phosphorylation may influence long-term clinical responsiveness to ChEIs.
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Acknowledgments
We should like to thank Professor Jeff Cummings for allowing us access to clinical data from his patients and Justine Pomakian and Carein Todd-Downing for their help in organising the databases. This work was supported by Janssen Pharmaceuticals and NIH P50 AG 16570 (HVV). The analysis used equipment provided by Alzheimer’s Research Trust (ART) and Bristol Research into Alzheimer’s and Care of the Elderly (BRACE). KAC is supported by an ART research fellowship. HVV is supported in part by the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine at the David Geffen School of Medicine at UCLA.
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Chalmers, K.A., Wilcock, G.K., Vinters, H.V. et al. Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer’s disease. J Neurol 256, 717–720 (2009). https://doi.org/10.1007/s00415-009-5000-2
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DOI: https://doi.org/10.1007/s00415-009-5000-2