Alzheimer’s pathogenic mechanisms and underlying sex difference

Abstract

Men are from Mars; Women are from Venus." But both can have Alzheimer's disease (AD), and it might be sex-specific. AD is a neurodegenerative disease and its prevalence is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5 years, plus there are more women aged 85 years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increasing body of evidence from preclinical and clinical studies as well as the complications in estimating incidence support the sex-specific biological mechanisms in diverging AD risk as an important adjunct explanation to the epidemiologic perspective. While some of the sex differences in AD prevalence are due to differences in longevity, other distinct biological mechanisms increase the risk and progression of AD in women. These risk factors include 1) deviations in brain structure and biomarkers, 2) psychosocial stress responses, 3) pregnancy, menopause, and sex hormones, 4) genetic background (i.e., APOE ), 5) inflammation, gliosis, and immune module (i.e., TREM2 ), and 6) vascular disorders. More studies focusing on the underlying biological mechanisms for this phenomenon are needed to better understand AD. This review presents the most recent data in sex differences in AD -the gateway to precision medicine, therefore, shaping expert perspectives, inspiring researchers to go Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation in new directions, and driving development of future diagnostic tools and treatments for AD in a more customized way.

Auditory sensory deprivation induced by noise exposure exacerbates cognitive decline in a mouse model of Alzheimer’s disease

“…Based on the mouse lifespan, the age of 3–6 months can be considered has a mature adult age ( Flurkey, 2007 ) and according to previous studies, including ours ( Chakroborty et al, 2019 ; Joseph et al, 2019 ; Cocco et al, 2020 ), 3×Tg-AD mice at the age of 2–3 months can be considered a model of preclinical AD, whereas the onset of AD phenotype manifests at 7–9 months. Sex differences in the prevalence, risk, and severity of AD as well as noise-induced hearing loss have been demonstrated in numerous clinical and animal studies ( Ferretti et al, 2018 ; Dumitrescu et al, 2019 ; Gür et al, 2019 ; Zhu et al, 2021 ), with greater susceptibility to AD ( Laws et al, 2016 ; Jiao et al, 2016 ; Koran et al, 2017 ; Yang et al, 2018 ) and lower susceptibility to noise-induced hearing loss ( Milon et al, 2018 ; Shuster et al, 2019 ) in females comparing to males. Considering the neuroprotective role of estrogens in noise damage, to better understand if and how hearing loss induced by noise exposure affected cognitive functions, we focused our study on male animals.…”

Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

“…Full-text articles were then obtained and reviewed thoroughly to identify studies reporting exosomal biomarkers in the blood samples of patients with AD. The inclusion criteria for the studies were as follows: (1) Articles that compared patients with AD and healthy controls; (2) articles that identified plasma or serum vesicles;…”

“…(1) Articles that used animal models; (2) articles that included a control group with other diseases, such as Down's Syndrome, HIV/AIDS, and Parkinson's disease; (3) articles not related to blood exosomes; (4) articles not related to protein biological biomarkers;…”

“…2 = 94%, p <0.001; 3B: I 2 = 88%, p <0.001; 3C: I 2 = 98%, p <0.001; 3D: I 2 = 97%, p < 0.001; 3E: I 2 = 93%, p <0.001; 3F: I 2 = 97%, p <0.001). Publication bias was evaluated using Egger's regression test.…”

“…Alzheimer's disease (AD) is a progressive neurodegenerative disorder [1]. The prevalence of AD in people over the age of 65 years is approximately 10%, and increases to 32% in people aged 85 years, showing increasing prevalence with age [2]. The estimated number of individuals with AD dementia is 5.8 million in the US, 9.1 million in the EU member states, and 50 million worldwide [1].…”