Effect of hormone replacement therapy on amyloid beta (Aß) plaque density in the rhesus macaque amygdala.

ABSTRACT

Background: Amyloid beta (Aß) plaque density was examined in the amygdala of rhesus macaques, to elucidate the influence of age, diet and hormonal environment. Methods: Luminex technology was used to measure cerebrospinal fluid (CSF) concentrations of Aß40 and Aß42 across three decades, while immunohistochemistry was used to examine Aß plaque density in the amygdala. Results: Aß40 was found to be the predominant isoform of Aß in the CSF, but neither Aß40 or Aß42 concentrations showed an age-related change, and the ratio of Aß42 to Aß40 showed only a marginal increase. Significantly fewer Aß plaques were detected in the amygdala of old ovariectomized animals if they received estradiol HRT (p < 0.001); similar results were obtained regardless of whether they had been maintained on a regular monkey chow for ∼48 months or on a high-fat, high-sugar, Western-style diet for ∼30 months. Conclusion: The results demonstrate that HRT involving estrogen can reduce Aß plaque load in a cognitive brain region of aged non-human primates. The results from this translational animal model may therefore have clinical relevance to the treatment of AD in post-menopausal women, whether used alone, or as a supplement to current pharmacological and monoclonal antibody-based interventions.