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O2‐05‐06: Pilot randomized controlled study of a histamine receptor inverse agonist in the symptomatic treatment of Alzheimer's disease
Author(s) -
Egan Michael,
Yaari Roy,
Liu Lian,
Ryan Michael,
Peng Yahong,
Lines Christopher,
Michelson David
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.871
Subject(s) - placebo , medicine , adverse effect , donepezil , concomitant , inverse agonist , randomized controlled trial , agonist , dementia , disease , receptor , pathology , alternative medicine
treatment improved latency, accuracy and probe trial deficits without reducing insoluble hippocampal tau or tangles. Soluble tau oligomers detected with p422S, PHF-1 and total tau antibodies were markedly reduced by curcumin. Tau Tg dependent losses of PSD-95, NR2B and GluR1 in the detergent lysis fraction (1% Triton X-100, 0.5% SDS) were prevented by curcumin. Tau Tg-induced elevations of PSD-95, NR2B and fyn in 2% SDS extracts of detergent were also prevented and associated with a large reduction in detergent fraction fyn. Conclusions: Elevated soluble tau oligomers, cognitive deficits, glutamate receptor dysregulation and tau partner fyn were effectively reduced with late intervention with oral curcumin. Because reduction of tau binding partner fyn can also protect glutamate receptor dysregulation-related cognitive deficits induced by Abeta oligomers, our results suggest possible common pathways and safe treatments for both Abeta and tau oligomer-mediated synaptic and cognitive deficits.