title: Imatinib treatment and Aβ42 in humans.
abstract: BACKGROUND
  The first-line treatment in chronic myeloid leukemia (CML), imatinib, has been shown to decrease the production of amyloid-β (Aβ) in vitro and in animal studies. However, whether imatinib has this effect in humans is not known.
  
  
  METHODS
  Plasma levels of Aβ42 were analyzed in sequential samples from CML patients treated with imatinib (n=51). The effect of imatinib on Aβ production was also investigated in human embryonic kidney 293 (HEK293) cells overexpressing the amyloid precursor protein (APP) with the Swedish mutation, in mouse primary cortical neurons and in human Down syndrome embryonic stem-cell-derived cortical neurons.
  
  
  RESULTS
  Twelve months of imatinib treatment did not lower plasma Aβ42 levels in CML patients, and imatinib treatment did not lead to less Aβ42 production in any of the in vitro models whereas β- and γ-secretase inhibitors did.
  
  
  CONCLUSIONS
  These data question the previously described role of imatinib in inhibiting amyloidogenic APP processing and as a drug candidate for AD.
authors: Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. Electronic address: bob.olsson@medic.gu.se.
authors: Bob
authors: B
authors: Olsson
authors: Service d'Hématologie Clinique, Hôpital de l'Archet, Nice, France.
authors: Laurence
authors: L
authors: Legros
authors: INSERM CIC 0802, CHU de Poitiers, Poitiers, France.
authors: François
authors: F
authors: Guilhot
authors: AstraZeneca R&D, Södertälje, Sweden.
authors: Kia
authors: K
authors: Strömberg
authors: Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors: James
authors: J
authors: Smith
authors: Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors: Frederick J
authors: FJ
authors: Livesey
authors: Quanterix Corporation, Cambridge, MA, USA.
authors: David H
authors: DH
authors: Wilson
authors: Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004314:Down Syndrome / Q000188:drug therapy / Q000503:physiopathology; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001549:Benzamides; D010446:Peptide Fragments; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C075222:amyloid beta-protein (1-42); D000068877:Imatinib Mesylate; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer's disease; Aβ42; CML; Imatinib; Plasma