Editorial: APOE4-associated heterogeneity in the pathogenesis of Alzheimer's disease DOI Creative Commons
Eileen Ruth S. Torres, G. William Rebeck, Tal Nuriel

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 19, 2024

descent over 12 years. They found that APOE4 carriers possessed greater associations between numerous baseline dietary factors/blood biomarkers and 12-year medial temporal lobe white matter integrity. On the other hand, while cardiovascular disease body mass index were also associated with integrity, this association was not affected by carrier status.Another important aspect of APOE4-associated AD risk is varying penetrance exists male female differing races/ethnicities [2; 3]. For example, it has been reported (regardless racial/ethnic background) possess an increased compared to their counterparts [2]. While reason for in women fully elucidated, previous studies have uncovered specific metabolic changes occur brain during menopause as a potential mediating factor [4; 5], several reporting early intervention hormone replacement therapy can reduce [6; 7]. topic, Wugalter et al. measured serum estrone (E1) estradiol (E2) levels postmenopausal from MsBrain cohort assess separate interactive estrogen, plasma biomarkers, status on regional volumes. The authors higher endogenous estrogen volumes only more severe biomarker profiles. However, effect driven non-carriers, suggesting do benefit similarly volumes.Balu investigated interaction sex, time mouse model APOE genotype AD. Utilizing EFAD AD, combination sex led earlier cognitive impairment mice, well Aβ pathology neuroinflammation. Interestingly, APOE3 mice similar indicating alone lead these mice. Meanwhile, Christensen utilized explore relationship obesity (a modifiable factor), therapy, deficits. When APOE3/3, APOE3/4, APOE4/4 fed high fat diet (HFD), overall impaired cognitively had worse function; however, APOE3/3 HFD regular chow-fed counterparts. treatment improved function performance all HFD-treated but benefitted most.Lastly, it's note heterogeneity already contributing real-world decisions, since are known be at developing Amyloid-Related Imaging Abnormalities (ARIA) being treated newly approved amyloid immunotherapies Leqembi Kisunla [8; 9]. In review article Foley Wilcock, highlighted three hypothesized mechanisms which may influencing ARIA risk: (1) reduced cerebrovascular (2) neuroinflammation immune dysregulation, (3) elevated cerebral angiopathy (CAA). Importantly, they detail how could pursued clinical preclinical studies, emphasizing usefulness therapies, now future, requires research community understand pathological mediated possession allele.

Language: Английский

Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease DOI Creative Commons
Constantinos O’Mahony, Oscar Hidalgo‐Lanussa, George E. Barreto

et al.

Experimental Gerontology, Journal Year: 2025, Volume and Issue: 200, P. 112679 - 112679

Published: Jan. 9, 2025

The increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration its complex etiology, with focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during endocrine transition emerge as early indicators AD pathology, including reduced glucose metabolism and increased amyloid-beta (Aβ) deposition. fluctuating environment, marked by declining estradiol levels estrogen receptor beta (ERβ) activity, further exacerbates this process. In context, here we explore potential forkhead box O3 (FOXO3) critical mediator linking metabolic disturbances to hormonal decline. We propose that FOXO3 plays key role intersection menopause AD, given dysregulation both patients women, modulating cellular through interactions AMPK/AKT/PI3K pathways. This relationship highlights between changes susceptibility. review aims open discussion FOXO3's contribution seen impact progression AD. Understanding functional menopause-associated could lead targeted therapeutic strategies, offering novel insights managing condition.

Language: Английский

Citations

1
Associations of dietary protein and amino acid intakes with disability-adjusted life years for Alzheimer's disease in Japanese people DOI Creative Commons
Kazuko Ishikawa‐Takata, Kazuki Fujiwara,

Takayuki Tanaka

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Background The number of patients with dementia is increasing worldwide. In Japan, the most significant reason recognized for people requiring nursing care. Protein one possible preventive nutrients dementia; however, adequate intake levels can differ according to usual protein intakes and sources. Objective This study examined relationships between disability-adjusted life years (DALYs) Alzheimer's disease or amino acid intakes. Methods Global Burden Disease Study data (DALYs each sex age group in year) de-identified individual records from National Health Nutrition Survey Japan (data 46,831 subjects) 2001 2019 were used. Multiple regression analyses conducted assess DALYs lifestyle factors sociodemographic index as confounding factors. Results Higher protein-to-energy ratios correlated lower women their 70 s (partial coefficient [Coeff.] = −349.488, p 0.034), men 60 (Coeff. −51.484), both sexes combined −26.696, 0.015) even after adjusting other nutrient Additionally, elevated isoleucine, lysine, tyrosine, histidine, arginine, alanine, asparagine, glycine −2.752 −0.141). Conclusions Adequate specific may be associated disease.

Language: Английский

Citations

0
The gut microbiota in menopause: Is there a role for prebiotic and probiotic solutions? DOI
Marrium Liaquat, Anne Marie Minihane, David Vauzour

et al.

Post Reproductive Health, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

The gut microbiota, comprising a diverse array of microorganisms in the gastrointestinal tract, has emerged as key player human health. Emerging research indicates that this microbial composition is influenced by sex. These sex differences are not necessarily static and likely alter across life course response to several factors including changing hormone profile. As such, menopause transition-a pivotal phase female ageing which profile changes dramatically receiving increasing attention. Declining estrogen occurs during appears influence may turn contribute menopause-related conditions such weight gain, bone health, cancer risk cognitive modulation through gut’s ‘estrobolome’, collection bacterial genes involved metabolism, offer explanation for some interindividual observed (e.g. length, symptoms disease risk). Therapeutic microbiota therefore represents potential approach towards managing menopausal symptoms. Indeed, prebiotics probiotics Lactobacillus have been shown increase diversity improve metabolic overall health women. However, evidence remains limited regarding specific underlying mechanisms, highlighting an urgent need focus area. This review summarizes current understanding microbiota’s role therapeutic interventions. Further into enable more effective, personalised treatments menopause-associated challenges, supporting women’s older ages.

Language: Английский

Citations

0
Editorial: APOE4-associated heterogeneity in the pathogenesis of Alzheimer's disease DOI Creative Commons
Eileen Ruth S. Torres, G. William Rebeck, Tal Nuriel

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 19, 2024

descent over 12 years. They found that APOE4 carriers possessed greater associations between numerous baseline dietary factors/blood biomarkers and 12-year medial temporal lobe white matter integrity. On the other hand, while cardiovascular disease body mass index were also associated with integrity, this association was not affected by carrier status.Another important aspect of APOE4-associated AD risk is varying penetrance exists male female differing races/ethnicities [2; 3]. For example, it has been reported (regardless racial/ethnic background) possess an increased compared to their counterparts [2]. While reason for in women fully elucidated, previous studies have uncovered specific metabolic changes occur brain during menopause as a potential mediating factor [4; 5], several reporting early intervention hormone replacement therapy can reduce [6; 7]. topic, Wugalter et al. measured serum estrone (E1) estradiol (E2) levels postmenopausal from MsBrain cohort assess separate interactive estrogen, plasma biomarkers, status on regional volumes. The authors higher endogenous estrogen volumes only more severe biomarker profiles. However, effect driven non-carriers, suggesting do benefit similarly volumes.Balu investigated interaction sex, time mouse model APOE genotype AD. Utilizing EFAD AD, combination sex led earlier cognitive impairment mice, well Aβ pathology neuroinflammation. Interestingly, APOE3 mice similar indicating alone lead these mice. Meanwhile, Christensen utilized explore relationship obesity (a modifiable factor), therapy, deficits. When APOE3/3, APOE3/4, APOE4/4 fed high fat diet (HFD), overall impaired cognitively had worse function; however, APOE3/3 HFD regular chow-fed counterparts. treatment improved function performance all HFD-treated but benefitted most.Lastly, it's note heterogeneity already contributing real-world decisions, since are known be at developing Amyloid-Related Imaging Abnormalities (ARIA) being treated newly approved amyloid immunotherapies Leqembi Kisunla [8; 9]. In review article Foley Wilcock, highlighted three hypothesized mechanisms which may influencing ARIA risk: (1) reduced cerebrovascular (2) neuroinflammation immune dysregulation, (3) elevated cerebral angiopathy (CAA). Importantly, they detail how could pursued clinical preclinical studies, emphasizing usefulness therapies, now future, requires research community understand pathological mediated possession allele.

Language: Английский

Citations

0