The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease

Abstract

In both men and women, age-related loss of sex steroid hormones has been linked to an increased risk for Alzheimer's disease (AD). The primary female hormone estrogen, and the primary male hormone testosterone have numerous protective effects in the brain relevant to the prevention of AD such as the promotion of neuron viability, reduction of β- amyloid accumulation and alleviation of tau hyperphosphorylation. Therefore it has been hypothesized that the precipitous loss of these hormones either through menopause or normal aging, can increase susceptibility to AD pathogenesis. This review will discuss the basic science research and epidemiological evidence largely supporting this hypothesis, as well as the estrogen-based hormone therapy clinical findings that have recently shed doubt on this theory. The complications associated with estrogen-based hormone therapy such as the inclusion of a progestogen, hormone responsiveness with age, and natural vs. synthetic hormones will be discussed. Further, we will outline the cancer risks facing both estrogen and testosterone-based hormone therapy. Most importantly, this review will discuss the present and future strategies to translate the neuroprotective properties of sex steroid hormones into safe and efficacious treatments for AD. One of the most promising translational tools thus far may be the development of selective estrogen and androgen receptor modulators. However, additional research is needed to optimize these and other translational tools towards the successful use of hormone therapies in both men and women to delay, prevent, and or treat AD.

A review on Alzheimer's disease pathophysiology and its management: an update

“…The primary female hormone estrogen and the 504 primary male hormone testosterone have numerous protective 505 effects in the brain relevant to the prevention of AD such as the 506 promotion of neuron viability, reduction of Ab accumulation and 507 alleviation of tau hyperphosphorylation. Complications are asso-508 ciated with estrogen-based hormone therapy such as the inclusion 509 of a progestrogen, hormone responsiveness with age, and natural 510 vs. synthetic hormones [100].…”

Women with the Alzheimer’s risk marker ApoE4 lose Aβ-specific CD4+ T cells 10–20 years before men

“…8,9 Both mouse and human studies have implicated menopause-related hormone deficiencies in this elevated risk profile. 46,47 Specifically, menopause causes rapid and significant decline in estrogen and progesterone, which could contribute to AD pathology; 48 further, estrogen levels significantly impact adaptive immunity. 49 Indeed, the earliest decline of Aβ-specific CD4 + T cells occurred in women who carried ApoE4 , reaching 50% of maximal around the age of 50, within the perimenopausal period for most women.…”

Modele funkcji poznawczych względem wybranych parametrów stanu funkcjonalnego tarczycy u kobiet po menopauzie

“…The theory of these changes that is most frequently considered is a rapid decline in sex hormones after menopause, and in consequence, the deterioration of cognitive functions. This theory has been confirmed by many studies, which showed the neuroprotective role of oestrogens and androgens on the nerve cells [12][13][14]. Nevertheless, investigations of the effect of oestrogen supplementation on cognitive functions after menopause did not bring about an unequivocal confirmation of this theory [15][16][17].…”