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Ann Clin Transl Neurol. 2019 Jun 6;6(6):1127-1133. doi: 10.1002/acn3.788. eCollection 2019 Jun.

No apparent effect of naproxen on CSF markers of innate immune activation.

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Faculty of Medicine McGill University Montréal Québec Canada.
Center for Studies on the Prevention of Alzheimer's Disease (StoP-AD) Douglas Mental Health University Institute Montréal Québec Canada.
Douglas Mental Health University Institute Research Centre Montréal Québec Canada.
McGill Centre for Studies in Aging Douglas Mental Health University Institute Montréal Québec Canada.


We studied 78 participants having a parental or multiple-sibling history of Alzheimer's disease (AD) in a two-year randomized placebo-controlled trial of naproxen 220 mg b.i.d. for mitigation of early AD pathogenesis. Naproxen was detected in cerebrospinal fluid at concentrations ~100 times lower than in plasma, but produced negligible change in immune markers. The repeated lack of benefit in AD prevention trials using naproxen and related drugs may reflect limited CNS permeability, lack of expected drug effects, or both. These findings suggest reconsideration of implications from results of AD prevention trials using anti-inflammatory drugs.

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