Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides.
Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid beta-amyloid (Abeta) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Abeta accumulation. Recent studies indicate that postmenopausal estrogen replacement therapy may prevent or delay the onset of AD. Here we present evidence that physiological levels of 17beta-estradiol reduce the generation of Abeta by neuroblastoma cells and by primary cultures of rat, mouse and human embryonic cerebrocortical neurons. These results suggest a mechanism by which estrogen replacement therapy can delay or prevent AD.
Xu
H
H
Laboratory of Molecular and Cellular Neuroscience, and Fisher Center for Research on Alzheimer Disease, The Rockefeller University, New York NY 10021, USA.
Gouras
G K
GK
Greenfield
J P
JP
Vincent
B
B
Naslund
J
J
Mazzarelli
L
L
Fried
G
G
Jovanovic
J N
JN
Seeger
M
M
Relkin
N R
NR
Liao
F
F
Checler
F
F
Buxbaum
J D
JD
Chait
B T
BT
Thinakaran
G
G
Sisodia
S S
SS
Wang
R
R
Greengard
P
P
Gandy
S
S
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D004958:Estradiol