Journal
NEUROLOGY
Volume 83, Issue 21, Pages 1930-1935Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000001017
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Funding
- AFI [09813]
- BMBF [AD-IG [FKZ01GS08130]]
- Bristol-Myers Squibb
- Janssen-Cilag
- Pfizer
- Eli Lilly
- Servier
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Objective: We investigated induction of alpha-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, Munchen-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of a-secretase-derived amyloid precursor protein (APPs-alpha). Methods: Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-alpha ratios calculated from the APPs-alpha levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as beta-amyloid 42 (A beta(42)) under treatment conditions. Results: The acitretin group showed a significant increase in CSF APPs-alpha levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03-0.72, p = 0.035) within this rather short treatment period. The synthetic retinoid acitretin was overall safe and well tolerated. Conclusions: Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in human patients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin's potential to serve as a novel therapeutic drug.
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