title: Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin.
abstract: OBJECTIVE
  We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase-derived amyloid precursor protein (APPs-α).
  
  
  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-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as β-amyloid 42 (Aβ42) under treatment conditions.
  
  
  RESULTS
  The acitretin group showed a significant increase in CSF APPs-α 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.
  
  
  METHODS
  This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-α levels.
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany. Kristina.Endres@unimedizin-mainz.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Endres
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Fahrenholz
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lotz
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lieb
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tüscher
authors.affiliation: From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fellgiebel
mesh_terms: D017255:Acitretin / Q000627:therapeutic use*; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D053829:Amyloid Precursor Protein Secretases; D017255:Acitretin