Ketogenic interventions restore cognition and modulate peripheral metabolic dysfunctions in Alzheimer's disease mouse models DOI Creative Commons

Paule E. H. M’Bra,

Laura K. Hamilton, Gaël Moquin‐Beaudry

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Summary Lifestyle factors modulate dementia risk. We investigated mechanisms of risk reduction by emerging dietary ketogenic interventions. show that distinct interventions, a medium-chain triglycerides (MCT)-enriched diet and carbohydrate-free, high-fat (CFHF), improve cognition dendritic spine density memory-associated hippocampal neurons in two mouse models Alzheimer’s disease (AD). Only the CFHF drove increased circulating ketones, suggesting underlying mechanisms. AD mice exhibited baseline diet-induced susceptibility to peripheral metabolic disturbances were improved MCT exacerbated diets. Prominent AD-associated dysregulation liver transcriptome was largely restored both but also downregulated lipogenic enzymes did not trigger CFHF-like inflammatory signature. Novel AD- plasmatic changes hormones lipid species identified. Thus, different interventions yield cognitive benefits while showing intervention-specific modulation defects, with implications for design therapeutic strategies.

Language: Английский

Review of Associations of Diabetes and Insulin Resistance With Brain Health in Three Harmonised Cohort Studies of Ageing and Dementia DOI Creative Commons
Roshni Biswas, Ana W. Capuano, Rupal I. Mehta

et al.

Diabetes/Metabolism Research and Reviews, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 1, 2025

ABSTRACT Diabetes increases the risk of dementia, and insulin resistance (IR) has emerged as a potential unifying feature. Here, we review published findings over past 2 decades on relation diabetes IR to brain health, including those related cognition neuropathology, in Religious Orders Study, Rush Memory Aging Project, Minority Research Study (ROS/MAP/MARS), three harmonised cohort studies ageing dementia at Alzheimer's Disease Center (RADC). A wide range participant data, information medical conditions such neuropsychological tests, well other clinical laboratory‐based data collected annually. Neuropathology are participants who agree autopsy death. Recent have measured additional peripheral multi‐omics. This summarises from RADC that investigate older adults cognition, omics health measures. Examining clinically diagnosed adults, our study found 65% increased disease (AD) individuals with compared without. Regarding cognitive function, consistently observed associations diabetes, both IR, worse declining performance global specific domains, particularly semantic memory perceptual speed. Studies utilising neuropathological showed infarcts, while measures, notably alpha serine/threonine‐protein kinase1 (AKT1), were associated infarcts AD pathology. Multi‐omics suggested shared causal genes pathways between dementia. epigenetic revealed risk, along distinct 5‐hydroxymethylcytosine signatures diabetes‐associated AD. Furthermore, utilised available impact neurological outcomes than reported worsening parkinsonian‐like signs diabetes. also explored factors for lower literacy decision‐making abilities elevated haemoglobin A1C levels, measure. Overall, findings, summarised this review, illustrate mechanistic insights into complex relationship health. These may important implications future research brain, prevention decline persons or

Language: Английский

Citations

2
Association of late‐life variability in hemoglobin A1C with postmortem neuropathologies DOI Creative Commons
Roshni Biswas, Ana W. Capuano, Rupal I. Mehta

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract INTRODUCTION To study the relationship of late‐life hemoglobin A1C (A1C) with postmortem neuropathology in older adults and without diabetes mellitus (DM). METHODS A total 990 participants from five cohort studies aging dementia at least two annually‐collected measures, who had autopsy. Neuropathologic evaluations documented cerebrovascular disease, Alzheimer's disease (AD), other pathologies. evaluate association mean variability (standard deviation [SD]) neuropathology, we used a series adjusted regression models. RESULTS Participants (mean age death = 90.8 years; education 15.8 76% women) six measurements on average. Mean was associated greater odds macroinfarcts (estimate 0.14; p 0.04) subcortical infarcts 0.16; 0.02). not pathology. were inversely AD DISCUSSION The average over time infarcts, Future should explore underlying mechanisms linking to dementia‐related neuropathologies. Highlights Hemoglobin (A1C), measure peripheral insulin resistance, is assess glycemic control. Higher macroscopic infarcts. Both inverse associations None varied by status.

Language: Английский

Citations

1
The effects of regular exercise on cognitive and cardiometabolic health in testicular cancer survivors subjected to platinum‐based chemotherapy DOI Open Access
Ali Amiri, Lucia Slobodová, Radka Klepochová

et al.

Andrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract Background Platinum‐based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy‐related toxicities. We examined the impact a 6‐month supervised aerobic‐strength training on cognitive health residual level platinum in cancer survivors. Methods Twenty‐eight middle‐aged (42.1 ± 7.6 years) survivors subjected platinum‐based (1–8 cycles, 0–24 years ago) were recruited into ( n = 20) control 8) groups. Effects whole‐body muscle metabolism, functions, cardiopulmonary fitness, plasma platinum, adiponectin examined. Results Exercise intervention improved fitness reduced visceral adiposity lipids, glucose (glycosylated hemoglobin) lipid (high‐density lipoprotein cholesterol) enhanced dynamics post‐exercise phosphocreatine recovery. Exercise‐related decline was paralleled by glycerophosphocholines metabolic flexibility during low‐intensity exercise, predicted training‐induced increase functions. Conclusions The resulted survivors, which providing evidence that structured brings multiple benefits

Language: Английский

Citations

0
Pharmacological Blocking of Adiponectin Receptors Induces Alzheimer’s Disease-like Neuropathology and Impairs Hippocampal Function DOI Creative Commons
Huihui Guo, Haining Ou,

Jiasui Yu

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1056 - 1056

Published: April 27, 2025

Background/Objectives: Previous studies have shown that adiponectin deficiency or blocking receptors (AdipoRs) in the brain can lead to an Alzheimer's disease (AD)-like neuropathology. While AdipoRs are abundantly expressed peripheral tissues, effects of these tissues on unclear. This study investigates impacts with a administration ADP400, antagonist peptide targets cognitive performance, hippocampal adult neurogenesis, and AD-like neuropathology mice. Methods: Adult mice were intraperitoneally administered ADP400 blocks continuously for 21 days, followed by battery behavioral test mood memory performance. Results: ADP400-treated exhibited impaired performance increased anxiety-like behaviors. Molecular analyses revealed heightened hyperphosphorylation tau β-amyloid levels, alongside decreased expression PP2A hippocampus, suggesting critical role Furthermore, treatment significantly reduced as indicated BrdU, Ki67, DCX staining. Inhibiting could accumulated levels. Conclusions: These findings highlight manipulation modulating function offering insights into potential therapeutic strategies AD related disorders.

Language: Английский

Citations

0
Brain phosphoproteomic analysis identifies diabetes‐related substrates in Alzheimer's disease pathology in older adults DOI Creative Commons
Ana W. Capuano, Vishal Sarsani, Shinya Tasaki

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract INTRODUCTION Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark AD pathology. However, comprehensive impact on patterns AD‐related phosphoprotein in human brain remains underexplored. METHODS We performed tandem mass tag–based phosphoproteome profiling post mortem prefrontal cortex samples from 191 deceased older adults with and without pathologic AD. RESULTS Among 7874 quantified phosphosites, microtubule‐associated (MAPT) phosphorylated at T529 T534 (isoform 8 T212 T217) were more abundant showed differential associations diabetes. Network analysis co‐abundance uncovered synergistic interactions between diabetes, one module exhibiting higher MAPT phosphorylation (15 phosphosites) another displaying lower MAP1B (22 phosphosites). DISCUSSION This study offers phosphoproteomics insights into shedding light mechanisms that can inform development therapeutics for Highlights The dementia is increased among living are Microtubule‐associated Phosphosite networks identified.

Language: Английский

Citations

1
Ketogenic interventions restore cognition and modulate peripheral metabolic dysfunctions in Alzheimer's disease mouse models DOI Creative Commons

Paule E. H. M’Bra,

Laura K. Hamilton, Gaël Moquin‐Beaudry

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Summary Lifestyle factors modulate dementia risk. We investigated mechanisms of risk reduction by emerging dietary ketogenic interventions. show that distinct interventions, a medium-chain triglycerides (MCT)-enriched diet and carbohydrate-free, high-fat (CFHF), improve cognition dendritic spine density memory-associated hippocampal neurons in two mouse models Alzheimer’s disease (AD). Only the CFHF drove increased circulating ketones, suggesting underlying mechanisms. AD mice exhibited baseline diet-induced susceptibility to peripheral metabolic disturbances were improved MCT exacerbated diets. Prominent AD-associated dysregulation liver transcriptome was largely restored both but also downregulated lipogenic enzymes did not trigger CFHF-like inflammatory signature. Novel AD- plasmatic changes hormones lipid species identified. Thus, different interventions yield cognitive benefits while showing intervention-specific modulation defects, with implications for design therapeutic strategies.

Language: Английский

Citations

0