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Chapter 27 - The role of gonadotropins and testosterone in the regulation of beta-amyloid metabolism

from Section 6 - Gonadotropin effects

Published online by Cambridge University Press:  06 July 2010

Eef Hogervorst
Affiliation:
Loughborough University
Victor W. Henderson
Affiliation:
Stanford University, California
Robert B. Gibbs
Affiliation:
University of Pittsburgh
Roberta Diaz Brinton
Affiliation:
University of Southern California
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Summary

Editors' introduction

Verdile and Martins review the relationship between dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis, reduced levels of testosterone in men, cognitive decline, and risk of Alzheimer's disease (AD). Regulation of testosterone and luteinizing hormone (LH) are tightly linked, and following reproductive senescence declines in sex hormones are coupled with elevated gonadotropin levels. Several studies have reported that compared to controls, men with AD and other dementias have lower serum testosterone levels. Testosterone has been shown to have a number of neuroprotective effects, including reducing oxidative stress and inflammatory processes, which are key events in the AD brain. While animal and in vitro analyses have provided support for the therapeutic potential of testosterone, definitive benefits of testosterone therapy remain to be determined. The APOE ε4 allele appears to be a determining factor in the association between testosterone and the risk of developing dementia in men. It appears that both testosterone and LH can impact beta-amyloid accumulation and AD pathogenesis, although the relative contributions of each hormone remain undefined. Verdile and Martins propose that combinational hormone therapy (HT) may prove to be more efficacious in the prevention of AD.

Type
Chapter
Information
Hormones, Cognition and Dementia
State of the Art and Emergent Therapeutic Strategies
, pp. 259 - 268
Publisher: Cambridge University Press
Print publication year: 2009

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