17beta-estradiol reduces plasma Abeta40 for HRT-naïve postmenopausal women with Alzheimer disease: a preliminary study.
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.
Baker
Laura D
LD
Geriatric Research, Education, and Clinical Center, the VA Puget Sound Health Care System, Seattle/Tacoma, WA, USA.
Sambamurti
Kumar
K
Craft
Suzanne
S
Cherrier
Monique
M
Raskind
Murray A
MA
Stanczyk
Frank Z
FZ
Plymate
Stephen R
SR
Asthana
Sanjay
S
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C419409:amyloid beta-protein (29-40); D004958:Estradiol