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 Aβ and Aβ across three decades, while immunohistochemistry was used to examine Aβ plaque density in the amygdala. Aβ was found to be the predominant isoform of Aβ in the CSF, but neither Aβ or Aβ concentrations showed an age-related change, and the ratio of Aβ to Aβ showed only a marginal increase. Significantly fewer Aβ plaques were detected in the amygdala of old ovariectomized animals if they received estradiol HRT ( < 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.