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

Amyloid beta (Aβ) plaque density was examined in the amygdala of rhesus macaques, to elucidate the influence of age, diet and hormonal environment.

Luminex technology was used to measure cerebrospinal fluid (CSF) concentrations of Aβ₄₀ and Aβ₄₂ across three decades, while immunohistochemistry was used to examine Aβ plaque density in the amygdala.

Aβ₄₀ was found to be the predominant isoform of Aβ in the CSF, but neither Aβ₄₀ or Aβ₄₂ concentrations showed an age-related change, and the ratio of Aβ₄₂ to Aβ₄₀ showed only a marginal increase. Significantly fewer Aβ 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.

The results demonstrate that HRT involving estrogen can reduce Aβ 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.