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| References
- Testosterone, the brain and psyche |
8
. Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R
et al. Testosterone reduces neuronal secretion of Alzheimer's
beta-amyloid peptides. Proc.Natl.Acad.Sci.U.S.A 2000;97:1202-5.
Abstract: Alzheimer's disease (AD) is characterized by the
age-related deposition of beta-amyloid (Abeta) 40/42 peptide
aggregates in vulnerable brain regions. Multiple levels of
evidence implicate a central role for Abeta in the pathophysiology
of AD. Abeta peptides are generated by the regulated cleavage
of an approximately 700-aa Abeta precursor protein (betaAPP).
Full-length betaAPP can undergo proteolytic cleavage either
within the Abeta domain to generate secreted sbetaAPPalpha
or at the N- and C-terminal domain(s) of Abeta to generate
amyloidogenic Abeta 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 17beta-estradiol
reduced the secretion of Abeta40/42 peptides, suggesting that
estrogen replacement therapy may protect women against the
development of AD by regulating betaAPP 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, sbetaAPPalpha,
and decreases the secretion of Abeta 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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