title: 17beta-estradiol reduces plasma Abeta40 for HRT-naïve postmenopausal women with Alzheimer disease: a preliminary study.
abstract: OBJECTIVE
  One mechanism to support the potentially beneficial effects of estrogen in the brain for postmenopausal women potentially involves the hormone's ability to favorably alter the processing of amyloid-precursor protein (APP), believed to play an important role in the pathobiology of Alzheimer disease (AD). The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Abeta40, for postmenopausal women with AD.
  
  
  METHODS
  In a placebo-controlled, double blind, parallel-group design study, 20 women were randomized to receive either 0.10 mg/day of transdermal 17beta-estradiol or a placebo for 8 weeks and were retrospectively evaluated as to whether basal levels of Abeta40 were affected by pre-study use of hormone replacement therapy (HRT). Blood samples were collected and cognitive tests were administered at baseline; at Weeks 3, 5, and 8 during treatment; and again 8 weeks after treatment termination.
  
  
  RESULTS
  For the group as a whole, plasma Abeta40 was not reliably reduced in response to short-term estradiol administration. For HRT-naïve subjects, baseline Abeta40 concentrations were higher than those of previous HRT users, and controlled estradiol administration significantly reduced plasma Abeta40 by the end of the 8-week treatment period.
  
  
  CONCLUSIONS
  These results provide preliminary clinical evidence to support an effect of estradiol on Abeta-processing for AD women who are HRT-naïve. This finding suggests that the hormone may serve as an Abeta-lowering agent for HRT-naïve AD women, which may, in turn, have ultimate ramifications for the progression of AD pathology.
authors.affiliation: Geriatric Research, Education, and Clinical Center, the VA Puget Sound Health Care System, Seattle/Tacoma, WA, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.forename: Kumar
authors.initials: K
authors.lastname: Sambamurti
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.forename: Monique
authors.initials: M
authors.lastname: Cherrier
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Plymate
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D017698:Postmenopause; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C419409:amyloid beta-protein (29-40); D004958:Estradiol