Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

Huaxi Xu; Gunnar K. Gouras; Jeffrey P. Greenfield; Bruno Vincent; Jan Naslund; Louis Mazzarelli; Gabriel Fried; Jasmina N. Jovanovic; Mary Seeger; Norman R. Relkin; Fang Liao; Frédéric Checler; Joseph D. Buxbaum; Brian T. Chait; Gopal Thinakaran; Sangram S. Sisodia; Rong Wang; Paul Greengard; Sam Gandy

doi:10.1038/nm0498-447

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

Huaxi Xu, Gunnar K. Gouras, Jeffrey P. Greenfield, Bruno Vincent, Jan Naslund, Louis Mazzarelli, Gabriel Fried, Jasmina N. Jovanovic, Mary Seeger, Norman R. Relkin, Fang Liao, Frédéric Checler, Joseph D. Buxbaum, Brian T. Chait, Gopal Thinakaran, Sangram S. Sisodia, Rong Wang, Paul Greengard, Sam Gandy

Research output: Contribution to journal › Article › peer-review

538 Scopus citations

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid ̄-amyloid (Aβ) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Aβ 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 17β-estradiol reduce the generation of Aβ 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.

Original language	English
Pages (from-to)	447-451
Number of pages	5
Journal	Nature Medicine
Volume	4
Issue number	4
DOIs	https://doi.org/10.1038/nm0498-447
State	Published - Apr 1998
Externally published	Yes

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Xu, H., Gouras, G. K., Greenfield, J. P., Vincent, B., Naslund, J., Mazzarelli, L., Fried, G., Jovanovic, J. N., Seeger, M., Relkin, N. R., Liao, F., Checler, F., Buxbaum, J. D., Chait, B. T., Thinakaran, G., Sisodia, S. S., Wang, R., Greengard, P., & Gandy, S. (1998). Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides. Nature Medicine, 4(4), 447-451. https://doi.org/10.1038/nm0498-447

@article{f8dca2a2513840139b49446507effc22,

title = "Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides",

abstract = "Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid{\= }-amyloid (Aβ) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Aβ 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 17β-estradiol reduce the generation of Aβ 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.",

author = "Huaxi Xu and Gouras, {Gunnar K.} and Greenfield, {Jeffrey P.} and Bruno Vincent and Jan Naslund and Louis Mazzarelli and Gabriel Fried and Jovanovic, {Jasmina N.} and Mary Seeger and Relkin, {Norman R.} and Fang Liao and Fr{\'e}d{\'e}ric Checler and Buxbaum, {Joseph D.} and Chait, {Brian T.} and Gopal Thinakaran and Sisodia, {Sangram S.} and Rong Wang and Paul Greengard and Sam Gandy",

year = "1998",

month = apr,

doi = "10.1038/nm0498-447",

language = "English",

volume = "4",

pages = "447--451",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "4",

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Xu, H, Gouras, GK, Greenfield, JP, Vincent, B, Naslund, J, Mazzarelli, L, Fried, G, Jovanovic, JN, Seeger, M, Relkin, NR, Liao, F, Checler, F, Buxbaum, JD, Chait, BT, Thinakaran, G, Sisodia, SS, Wang, R, Greengard, P & Gandy, S 1998, 'Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides', Nature Medicine, vol. 4, no. 4, pp. 447-451. https://doi.org/10.1038/nm0498-447

TY - JOUR

T1 - Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

AU - Xu, Huaxi

AU - Gouras, Gunnar K.

AU - Greenfield, Jeffrey P.

AU - Vincent, Bruno

AU - Naslund, Jan

AU - Mazzarelli, Louis

AU - Fried, Gabriel

AU - Jovanovic, Jasmina N.

AU - Seeger, Mary

AU - Relkin, Norman R.

AU - Liao, Fang

AU - Checler, Frédéric

AU - Buxbaum, Joseph D.

AU - Chait, Brian T.

AU - Thinakaran, Gopal

AU - Sisodia, Sangram S.

AU - Wang, Rong

AU - Greengard, Paul

AU - Gandy, Sam

PY - 1998/4

Y1 - 1998/4

N2 - Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid ̄-amyloid (Aβ) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Aβ 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 17β-estradiol reduce the generation of Aβ 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.

AB - Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid ̄-amyloid (Aβ) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Aβ 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 17β-estradiol reduce the generation of Aβ 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.

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U2 - 10.1038/nm0498-447

DO - 10.1038/nm0498-447

M3 - Article

C2 - 9546791

AN - SCOPUS:0031946864

SN - 1078-8956

VL - 4

SP - 447

EP - 451

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

Abstract

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