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Testosterone reduces neuronal secretion of Alzheimer's β-amyloid peptides

Gouras, Gunnar K. LU orcid ; Xu, Huaxi ; Gross, Rachel S. ; Greenfield, Jeffrey P. ; Hai, Bing ; Wang, Rong and Greengard, Paul (2000) In Proceedings of the National Academy of Sciences of the United States of America 97(3). p.1202-1205
Abstract

Alzheimer's disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ peptides are generated by the regulated cleavage of an ≃700-aa Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the A β domain to generate secreted sβAPPα or at the N- and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. We previously reported that treating cultured neurons with 17β-estradiol reduced... (More)

Alzheimer's disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ peptides are generated by the regulated cleavage of an ≃700-aa Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the A β domain to generate secreted sβAPPα or at the N- and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. We previously reported that treating cultured neurons with 17β-estradiol reduced the secretion of Aβ40/42 peptides, suggesting that estrogen replacement therapy may protect women against the development of AD by regulating βAPP metabolism. Increasing evidence indicates that testosterone, especially bioavailable testosterone, decreases with age in older men and in postmenopausal women. We report here that treatment with testosterone increases the secretion of the nonamyloidogenic APP fragment, sβAPPα, and decreases the secretion of Aβ peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that testosterone supplementation in elderly men may be protective in the treatment of AD.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences of the United States of America
volume
97
issue
3
pages
1202 - 1205
publisher
National Academy of Sciences
external identifiers
  • pmid:10655508
  • scopus:0033950794
ISSN
0027-8424
DOI
10.1073/pnas.97.3.1202
language
English
LU publication?
no
id
7c00cbe7-5949-43fd-9d21-664347a29257
date added to LUP
2020-02-20 14:28:31
date last changed
2024-04-17 05:15:58
@article{7c00cbe7-5949-43fd-9d21-664347a29257,
  abstract     = {{<p>Alzheimer's disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ peptides are generated by the regulated cleavage of an ≃700-aa Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the A β domain to generate secreted sβAPPα or at the N- and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. We previously reported that treating cultured neurons with 17β-estradiol reduced the secretion of Aβ40/42 peptides, suggesting that estrogen replacement therapy may protect women against the development of AD by regulating βAPP metabolism. Increasing evidence indicates that testosterone, especially bioavailable testosterone, decreases with age in older men and in postmenopausal women. We report here that treatment with testosterone increases the secretion of the nonamyloidogenic APP fragment, sβAPPα, and decreases the secretion of Aβ peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that testosterone supplementation in elderly men may be protective in the treatment of AD.</p>}},
  author       = {{Gouras, Gunnar K. and Xu, Huaxi and Gross, Rachel S. and Greenfield, Jeffrey P. and Hai, Bing and Wang, Rong and Greengard, Paul}},
  issn         = {{0027-8424}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{3}},
  pages        = {{1202--1205}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Testosterone reduces neuronal secretion of Alzheimer's β-amyloid peptides}},
  url          = {{http://dx.doi.org/10.1073/pnas.97.3.1202}},
  doi          = {{10.1073/pnas.97.3.1202}},
  volume       = {{97}},
  year         = {{2000}},
}