Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Academic Article uri icon

Overview

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.

publication date

  • February 1, 2000

Research

keywords

  • Alzheimer Disease
  • Amyloid beta-Protein Precursor
  • Testosterone

Identity

PubMed Central ID

  • PMC15568

Scopus Document Identifier

  • 0033950794

Digital Object Identifier (DOI)

  • 10.1073/pnas.97.3.1202

PubMed ID

  • 10655508

Additional Document Info

volume

  • 97

issue

  • 3