The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5771 - 5788

Published: June 28, 2024

Abstract Over the past decades, accumulating evidence suggests that gut microbiome exerts a key role in Alzheimer's disease (AD). The Association Workgroup is updating diagnostic criteria for AD, which changed profiles and categorization of biomarkers from “AT(N)” to “ATNIVS.” Previously, most studies focus on correlation between amyloid beta deposition (“A”), initial AD pathological feature triggering “downstream” tauopathy neurodegeneration. However, limited research investigated interactions other pathogenesis (“TNIVS”). In this review, we summarize current findings microbial characteristics whole spectrum AD. Then, describe association with updated biomarker categories pathogenesis. addition, outline microbiome‐related therapeutic strategies Finally, discuss issues field future directions. Highlights new revised (AD) proposed by have associations are described. Current summarized. Therapeutic based proposed.

Language: Английский

---

Roseburia intestinalis Supplementation Could Reverse the Learning and Memory Impairment and m6A Methylation Modification Decrease Caused by 27-Hydroxycholesterol in Mice

Nutrients, Journal Year: 2024, Volume and Issue: 16(9), P. 1288 - 1288

Published: April 26, 2024

The abnormality in N6-methyladenosine (m6A) methylation is involved the course of Alzheimer’s disease (AD), while intervention 27-Hydroxycholesterol (27-OHC) can affect m6A modification brain cortex. Disordered gut microbiota a key link 27-OHC leading to cognitive impairment, and further studies have found that abundance Roseburia intestinalis significantly reduced under 27-OHC. This study aims investigate association 27-OHC, gut, learning memory ability injury. In this study, 9-month-old male C57BL/6J mice were treated with antibiotic cocktails for 6 weeks sweep intestinal flora, followed by or normal saline subcutaneous injection, then gavage applied mouse. level brain, barrier function, measured. From results, we observed impairs causing disturbance expression methylation-related enzymes reducing cortex, finally leads impairment. However, supplementation could reverse negative effects mentioned above. suggests 27-OHC-induced impairment might be linked disturbance, intestinalis, as probiotic great potential, damage caused research help reveal mechanism neural provide important scientific evidence future use neuroprotection.

Language: Английский

---

Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 12, 2024

Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with decline. This study explored link among cognition, gut microbiota uptake based on fecal transplantation from mild impairment individuals (MCI-FMT) investigated whether similar were involved 27-hydroxycholesterol (27-OHC)-induced Our results showed that MCI-FMT mice exhibited learning memory decline morphological lesions brain colon tissues. There reduced

Language: Английский

---

The mechanisms, hallmarks, and therapies for brain aging and age-related dementia

Science Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

---

A panel of altered blood oxysterols in patients with mild cognitive impairment: A novel combined diagnostic marker

Pharmacological Research, Journal Year: 2025, Volume and Issue: 213, P. 107661 - 107661

Published: Feb. 20, 2025

Perturbed cholesterol metabolism may play an important role in the development of dementia and its preclinical stage, mild cognitive impairment (MCI). Oxysterols, metabolites generated during oxidation, also appear to be risk factors for MCI. Therefore, we aimed investigate if metabolic profile blood oxysterols could used characterize MCI risk. This cross-sectional study incorporated 501 participants-253 patients with 248 cognitively normal controls. Serum levels 22 free were measured, a set 27 oxysterol-related gene polymorphisms was genotyped. Five [27-hydroxycholesterol (27-OHC), 27-OHC periphery-derived metabolite 3β-hydroxy-5-cholestenoic acid (27-CA) brain-derived 7α-hydroxy-3-oxo-4-cholestenoic (7-HOCA), 4β-hydroxycholesterol (4β-OHC); 4α-hydroxycholesterol (4α-OHC)] twenty-two detected serum significantly differed between controls, greatly distinguishing from control individuals (AUC=0.834, 95% CI: 0.804-0.866). Association analyses demonstrated significant correlations these candidate oxysterol biomarkers younger age, higher lipids, worse performance, monounsaturated fatty intake. panel as highlighted essential pathogenesis early prevention. (The registered Chinese Clinical Trial Registry ChiCTR-OOC-17011882).

Language: Английский

---

Cholesterol-modifying strategies for alzheimer disease: promise or fallacy?

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

As the world population ages, Alzheimer disease (AD) prevalence increases. However, understanding of AD etiology continues to evolve, and pathophysiological processes involved are only partially elucidated. One compound suspected play a role in development progression is cholesterol. Several lines evidence support this connection, yet it remains unclear whether cholesterol-modifying strategies have potential applications clinical management AD. A deep literature search using PubMed was performed prepare narrative review. The search, early 2024, inclusive from 1990 2024. After providing an overview cholesterol metabolism, study summarizes key preclinical studies that investigated therapies laboratory models It also past current trials testing specific targets modulated by anti-cholesterol patients. Based on epidemiological mechanistic studies, likely plays etiology. use could be promising treatment approach if administered at presymptomatic phases, but unlikely efficient mild, moderate, late stages. recommendations provided for hypercholesterolemia

Language: Английский

---

The Link Between Oxysterols and Gut Microbiota in the Co-Dysfunction of Cognition and Muscle

Nutrients, Journal Year: 2025, Volume and Issue: 17(7), P. 1277 - 1277

Published: April 6, 2025

Background/Objectives: Alterations of oxysterols and gut microbiota have been recognized as indicators affecting mild cognitive impairment (MCI) sarcopenia, respectively, whereas their association with co-dysfunction has not investigated. Methods: In this study, a total 1035 individuals were divided into Control (n = 264), MCI 435), possible sarcopenia (MPS, n 336) groups. Cognition muscle indexes, serum oxysterols, measured. Spearman's rank coefficients calculated to determine correlations. Results: Performances global multidimensional tests was successively worse in the Control, MCI, MPS Longer duration five-time chair stand test, lower 6-meter walk speed, handgrip strength observed group, along increased 27-hydroxycholesterol (27-OHC) 5α,6α-epoxycholesterol decreased 5α-Cholest-8(14)-ene-3β,15α-diol (15-HC). Higher concentrations amyloid precursor protein (APP), neurofilament, C-terminal agrin fragment (CAF) discovered The α-diversity group remarkably decreased, followed by shifted abundance microbial taxa, such Alistipes Rikenellaceae. Multiple significant correlations found between cognition indexes oxysterols. Conclusions: Our study indicates that are prominently involved muscle.

Language: Английский

---

Systematic review and meta-analysis of microbiota-gut-astrocyte axis perturbation in neurodegeneration, brain injury, and mood disorders

Brain Behavior & Immunity - Health, Journal Year: 2025, Volume and Issue: unknown, P. 101013 - 101013

Published: May 1, 2025

Language: Английский

---

27-Hydroxycholesterol in cancer development and drug resistance

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: May 22, 2025

27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as selective oestrogen receptor (ER) modulator and ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial context-dependent. In this review, we provide an overview the biosynthesis metabolism explore cancer-associated signalling, with particular focus on ER- LXR-mediated pathways. Given tissue-specific dual 27HC, discuss differential impact across various cancer types. Furthermore, sort out 27HC-contributed drug resistance mechanisms from perspectives efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, metabolic reprogramming. Finally, highlight chemical inhibitors to mitigate 27HC-driven progression resistance. This review offers updated biology, setting stage future development targeted therapeutics.

Language: Английский

---

18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 196, P. 112577 - 112577

Published: Sept. 10, 2024

Total cholesterol (TC) and the oxidation product 27-hydroxycholesterol (27-OHC) are both increased in elderly. Accumulating evidence has linked 27-OHC to glucose metabolism brain, while docosahexaenoic acid (DHA) been shown positively regulate levels. However, it is unclear whether DHA may affect brain by regulating In this study, we hypothesized that supplementation would modulate TC levels reduce levels, thereby improving SAMP8 mice. The mice were assigned into Control group dietary group. study evaluated brain. results showed decreased serum of TC, low-density lipoprotein (LDL-C), high-density (HDL-C); improved glucose-corrected standardized uptake value cortex, hippocampus, whole regions conclusion, could composition level 27-OHC,

Language: Английский

---