TY - JOUR
T1 - Effect of hormone replacement therapy on amyloid beta (Aβ) plaque density in the rhesus macaque amygdala
AU - Appleman, Maria Luisa
AU - Thomas, Jeremy L.
AU - Weiss, Alison R.
AU - Nilaver, Benjamin I.
AU - Cervera-Juanes, Rita
AU - Kohama, Steven G.
AU - Urbanski, Henryk F.
N1 - Publisher Copyright:
Copyright © 2024 Appleman, Thomas, Weiss, Nilaver, Cervera-Juanes, Kohama and Urbanski.
PY - 2023
Y1 - 2023
N2 - 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: 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. 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.
AB - 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: 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. 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.
KW - Alzheimer’s disease
KW - aging
KW - amyloid plaques
KW - hormone replacement therapy (HRT)
KW - menopause
KW - rhesus macaque
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U2 - 10.3389/fnagi.2023.1326747
DO - 10.3389/fnagi.2023.1326747
M3 - Article
AN - SCOPUS:85182702327
SN - 1663-4365
VL - 15
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 1326747
ER -