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Review
. 2022 Oct 19:13:1021796.
doi: 10.3389/fendo.2022.1021796. eCollection 2022.

Menopause and development of Alzheimer's disease: Roles of neural glucose metabolism and Wnt signaling

Paulina Villaseca  1 , Pedro Cisternas  2 , Nibaldo C Inestrosa  1   3
Affiliations
Review

Menopause and development of Alzheimer's disease: Roles of neural glucose metabolism and Wnt signaling

Paulina Villaseca et al. Front Endocrinol (Lausanne). .

Abstract

Late onset Alzheimer´s disease (AD) is a neurodegenerative disease with gender differences in its onset and progression, being the prevalence predominant in women and at an earlier age than in men. The pathophysiology of the menopausal condition has been associated to this dementia, playing major roles regarding both endocrine and glucose metabolism changes, amongst other mechanisms. In the current review we address the role of estrogen deficiency in the processes involved in the development of AD, including amyloid precursor protein (APP) processing to form senile plaques, Tau phosphorylation forming neurofibrillary tangles, Wnt signaling and AD neuropathology, the role of glucose brain metabolism, Wnt signaling and glucose transport in the brain, and our research contribution to these topics.

Keywords: APP - amyloid precursor protein; alzheimer´s disease; estrogen; glucose brain metabolism; menopause; tau phosphorylation; wnt signaling.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
How factors are interrelated and their role in AD (Estrogen, Wnt signaling, glucose metabolism and neurodegeneration). Scheme integrating the actions of Wnt signaling, Estrogen levels, Aβ peptide synthesis and brain glucose uptake in the Adult Female as opposed to the Menopause status: In the Adult Female, estrogen (E2) inhibits the synthesis of Dkk1 (a physiological antagonist of Wnt canonical signaling) (23), thus promoting the activation of Wnt canonical signaling and leading to a decrease of Aβ peptide synthesis, an increase in synaptic protection and development of dendritic spines; in parallel, also leading to increased brain glucose uptake. In Menopause, the decrease of E2 induces an increase of Dkk1 and the consequent decrease in Wnt signaling activity, that lead to an increase and aggregation of Aβ peptide and neuronal damage, as the loss of dendritic spines by the accumulation of plaques; in parallel, the decrease in Wnt signaling activity, decreases brain glucose metabolism.
See this image and copyright information in PMC

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