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

Front Aging Neurosci. 2024 Jan 11:15:1326747. doi: 10.3389/fnagi.2023.1326747. eCollection 2023.

Abstract

Background: Amyloid beta (Aβ) 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 Aβ40 and Aβ42 across three decades, while immunohistochemistry was used to examine Aβ plaque density in the amygdala.

Results: 40 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.

Conclusion: 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.

Keywords: Alzheimer’s disease; aging; amyloid plaques; hormone replacement therapy (HRT); menopause; rhesus macaque.