title: Protein Expression of BACE1 is Downregulated by Donepezil in Alzheimer's Disease Platelets.
abstract: Abnormal amyloid-β protein precursor (AβPP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for AβPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AβPP-related molecules in platelets may be regarded as peripheral markers of AD.
  
  
  
  We sought to determine the protein expression of the AβPP secretases (ADAM10, BACE1, and PSEN1) and AβPP ratio in platelets of patients with mild or moderate AD compared to healthy controls. We further determined whether the protein expression of these markers might be modified by chronic treatment with donepezil.
  
  
  
  Platelet samples were obtained from patients and controls at baseline and after 3 and 6 months of continuous treatment with therapeutic doses of donepezil. The protein expression of platelet markers was determined by western blotting.
  
  
  
  AD patients had a significant decrease in AβPP ratio, ADAM10, and PSEN1 compared to controls at baseline, but these differences were not modified by the treatment. Nonetheless, a significant reduction in the protein expression of BACE1 was observed in patients treated with donepezil for 6 months.
  
  
  
  Our results corroborate previous findings from our group and others of decreased AβPP ratio and protein expression of ADAM10 in AD. We further show that PSEN1 is decreased in AD platelets, and that the protein expression of BACE1 is downregulated by chronic treatment with donepezil. This effect may be interpreted as evidence of disease modification.
authors.forename: Tamires Alves
authors.initials: TA
authors.lastname: Sarno
authors.forename: Leda Leme
authors.initials: LL
authors.lastname: Talib
authors.forename: Helena Passarelli Giroud
authors.initials: HP
authors.lastname: Joaquim
authors.forename: Jessyka Maria de França
authors.initials: JM
authors.lastname: Bram
authors.forename: Wagner Farid
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Orestes Vicente
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D053764:Presenilin-1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D002800:Cholinesterase Inhibitors; D007189:Indans; C508853:PSEN1 protein, human; D010880:Piperidines; D053764:Presenilin-1; D000077265:Donepezil; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D000072197:ADAM10 Protein
keywords: ADAM10; Alzheimer’s disease; BACE1; PSEN1; amyloid-β protein precursor; donepezil; platelet; secretases