Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease

Emily R. Rosario, Jenna C. Carroll, Salvatore Oddo, Frank M. LaFerla, Christian J. Pike

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Normal age-related testosterone depletion in men is a recently identified risk factor for Alzheimer's disease (AD), but how androgen loss affects the development of AD is unclear. To investigate the relationship between androgen depletion and AD, we compared how androgen status affects the progression of neuropathology in the triple transgenic mouse model of AD (3xTg-AD). Adult male 3xTg-AD mice were sham gonadectomized (GDX) or GDX to deplete endogenous androgens and then exposed for 4 months to either the androgen dihydrotestosterone (DHT) or to placebo. In comparison to gonadally intact 3xTg-AD mice, GDX mice exhibited robust increases in the accumulation of β-amyloid (Aβ), the protein implicated as the primary causal factor in AD pathogenesis, in both hippocampus and amygdala. In parallel to elevated levels of Aβ, GDX mice exhibited significantly impaired spontaneous alternation behavior, indicating deficits in hippocampal function. Importantly, DHT treatment of GDX 3xTg-AD mice attenuated both Aβ accumulation and behavioral deficits. These data demonstrate that androgen depletion accelerates the development of AD-like neuropathology, suggesting that a similar mechanism may underlie the increased risk for AD in men with low testosterone. In addition, our finding that DHT protects against acceleration of AD-like neuropathology predicts that androgen-based hormone therapy may be a useful strategy for the prevention and treatment of AD in aging men.

Original languageEnglish (US)
Pages (from-to)13384-13389
Number of pages6
JournalJournal of Neuroscience
Volume26
Issue number51
DOIs
StatePublished - Dec 20 2006
Externally publishedYes

Fingerprint

Transgenic Mice
Androgens
Alzheimer Disease
Dihydrotestosterone
Neuropathology
Testosterone
Serum Amyloid A Protein
Amygdala
Hippocampus
Therapeutics
Placebos
Hormones

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Dihydrotestosterone
  • Neuropathology
  • Spontaneous alternation
  • Testosterone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. / Rosario, Emily R.; Carroll, Jenna C.; Oddo, Salvatore; LaFerla, Frank M.; Pike, Christian J.

In: Journal of Neuroscience, Vol. 26, No. 51, 20.12.2006, p. 13384-13389.

Research output: Contribution to journalArticle

Rosario, Emily R. ; Carroll, Jenna C. ; Oddo, Salvatore ; LaFerla, Frank M. ; Pike, Christian J. / Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 51. pp. 13384-13389.
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