Neuroinflammation in Alzheimer disease

Nature reviews. Immunology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

Язык: Английский

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Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review

Biomedicines, Год журнала: 2025, Номер 13(1), С. 115 - 115

Опубликована: Янв. 7, 2025

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery quality of life. As the aging population grows, rising number patients has made PND an urgent clinical challenge. Despite increasing research efforts, pathophysiological mechanisms underlying remain inadequately characterized, underscoring need for more integrated framework to guide targeted interventions. To better understand molecular therapeutic targets PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches PubMed, Embase, Cochrane Library, Web Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, white matter lesions as central pathophysiology, with particular parallels encephalocele- sepsis-associated impairments. Among these, mediated pathways such NLRP3 inflammasome blood-brain barrier disruption, emerges pivotal driver, triggering cascades exacerbate neuronal injury. Oxidative stress synergistically amplify these effects, while imbalances alterations, including lesions, contribute synaptic decline. Anesthetic agents modulate interconnected pathways, exhibiting both protective detrimental effects. Propofol dexmedetomidine demonstrate neuroprotective properties suppressing neuroinflammation microglial activation, whereas inhalational anesthetics like sevoflurane intensify inflammatory responses. Ketamine, its anti-inflammatory potential, offers promise but requires further evaluation determine long-term safety efficacy. By bridging insights practice, highlights critical role personalized anesthetic strategies mitigating improving patients. It aims inform future decision-making address multifaceted

Язык: Английский

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Plasma biomarkers for Alzheimer’s and related dementias: A review and outlook for clinical neuropsychology

Archives of Clinical Neuropsychology, Год журнала: 2024, Номер 39(3), С. 313 - 324

Опубликована: Март 22, 2024

Recent technological advances have improved the sensitivity and specificity of blood-based biomarkers for Alzheimer's disease related dementias. Accurate quantification amyloid-ß peptide, phosphorylated tau (pTau) isoforms, as well markers neurodegeneration (neurofilament light chain [NfL]) neuro-immune activation (glial fibrillary acidic protein [GFAP] chitinase-3-like 1 [YKL-40]) in blood has allowed researchers to characterize neurobiological processes at scale a cost-effective minimally invasive manner. Although currently used primarily research purposes, these potential be highly impactful clinical setting - aiding diagnosis, predicting risk, monitoring progression. Whereas plasma NfL shown promise non-specific marker neuronal injury, pTau181, pTau217, pTau231, GFAP demonstrated desirable levels identification individuals with pathology dementia. In this forward looking review, we (i) provide an overview most commonly dementias, (ii) discuss how comorbid medical conditions, demographic, genetic factors can inform interpretation biomarkers, (iii) describe ongoing efforts move into clinic, (iv) highlight central role that neuropsychologists may play contextualizing communicating biomarker results patients.

Язык: Английский

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Molecular Mechanisms Linking Osteoarthritis and Alzheimer’s Disease: Shared Pathways, Mechanisms and Breakthrough Prospects

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 3044 - 3044

Опубликована: Март 6, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative mostly affecting the elderly population. It characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aβ) peptides aggregation hyperphosphorylated TAU have been established as major pathological hallmarks disease, other factors such interaction genetic environmental are believed contribute development progression AD. In general, patients initially present mild forgetfulness difficulty in forming new memories. As it progresses, there significant impairments problem solving, social interaction, speech overall function affected individual. Osteoarthritis (OA) most recurrent form arthritis widely acknowledged whole-joint distinguished degeneration erosion joint cartilage accompanying synovitis subchondral bone changes can prompt peripheral inflammatory responses. Also predominantly elderly, OA frequently embroils weight-bearing joints knees, spine hips leading pains, stiffness diminished mobility, which turn significantly impacts patient’s standard life. Both infirmities co-occur older adults result independent factors, multiple health conditions common old age. Additionally, risk genetics, lifestyle changes, age chronic inflammation may both some individuals. Besides localized low-grade inflammation, notable systemic prompted play role AD pathogenesis. Studies explored relationships between inflammatory-associated diseases like obesity, hypertension, dyslipidemia, diabetes mellitus Given dementia shares similar with OA—both being age-related diseases, indeed serve factor for This work aims review literature on molecular mechanisms linking pathologies, explore potential connections these alongside future prospects innovative treatments.

Язык: Английский

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Epigenetic control of microglial immune responses

Immunological Reviews, Год журнала: 2024, Номер 323(1), С. 209 - 226

Опубликована: Март 16, 2024

Summary Microglia, the major population of brain‐resident macrophages, are now recognized as a heterogeneous comprising several cell subtypes with different (so far mostly supposed) functions in health and disease. A number studies have performed molecular characterization these microglial activation states over last years making use “omics” technologies, that is transcriptomics, proteomics and, less frequently, epigenomics profiling. These approaches offer possibility to identify disease mechanisms, discover novel diagnostic biomarkers, develop new therapeutic strategies. Here, we focus on epigenetic profiling means understand immune responses beyond what other omics methods can offer, is, revealing past present responses, gene regulatory networks potential future response trajectories, defining subtype‐specific relevance through mapping non‐coding genetic variants. We review current knowledge field regarding regulation identity function, provide an exemplary analysis demonstrates advantages performing joint transcriptomic epigenomic single cells discuss how comprehensive analyses may enhance our understanding pathophysiology.

Язык: Английский

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Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is unknown. Determining important anticipating the potential future incidence To begin to do this, we measured plasma biomarkers linked Alzheimer’s disease pathology in UK Biobank before and after serology-confirmed SARS-CoV-2 infections. infection was associated with β-amyloid pathology: reduced Aβ42:Aβ40 ratio and, more vulnerable participants, lower Aβ42 higher pTau-181. The biomarker changes were greater participants who had been hospitalized COVID-19 or reported hypertension previously. We showed brain structural imaging patterns disease, cognitive test scores poorer overall health evaluations. Our data from post hoc case–control matched study thus provide observational evidence can be older adults. While these results not establish causality, they suggest (and possibly other inflammatory diseases) risk disease.

Язык: Английский

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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(8), С. 5720 - 5739

Опубликована: Июнь 2, 2024

Abstract Alzheimer's disease (AD) is a neurodegenerative that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between brain and bone, but interaction bone AD remains unclear. In this review, we summarize human of association provide an overview their interactions underlying mechanisms AD. We review effects on from aspects pathogenic proteins, risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), autonomic nervous system. Correspondingly, elucidate involvement pathogenesis AD, including bone‐derived hormones, marrow‐derived cells, EVs, inflammation. On basis brain, propose potential strategies for management with hope offering novel perspectives its prevention treatment. Highlights The along consequent changes may involve disturbing homeostasis. Degenerative disorders influence progression through series pathophysiological mechanisms. Therefore, relevant intervention be beneficial comprehensive

Язык: Английский

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Crosstalk between peripheral inflammation and brain: focus on the responses of microglia and astrocytes to peripheral challenge

Neurochemistry International, Год журнала: 2024, Номер unknown, С. 105872 - 105872

Опубликована: Окт. 1, 2024

Язык: Английский

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Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100128 - 100128

Опубликована: Март 1, 2025

The swift rise in the prevalence of Alzheimer's disease (AD) alongside its significant societal and economic impact has created a pressing demand for effective interventions treatments. However, there are no available treatments that can modify progression disease. Eight AD brain tissues datasets three blood were obtained. Consensus clustering was utilized as method to discern various subtypes AD. Then, module genes screened using weighted correlation network analysis (WGCNA). Furthermore, screening hub conducted through machine-learning analyses. Finally, A comprehensive systematic approach druggable genome-wide Mendelian randomization (MR) conducted. Two subclasses identified, namely cluster.A cluster.B. levels gamma secretase activity, beta amyloid-beta 42 found be significantly elevated patients classified within cluster when compared those B. by utilizing differentially expressed shared among these clusters, along with identifying applying WGCNA subtypes, we able develop scoring system referred DG.score. This demonstrated remarkable predictive capability evaluated against multiple datasets. Besides, total 30 distinct may serve potential drug targets identified across at least one investigated, whether derived from samples or Among genes, specific candidates considered (LIMK2, MAPK8, NDUFV2) expression both tissues. our research also revealed association between LIMK2 concentrations CSF Aβ (OR 1.526 (1.155-2.018)), p-tau 1.106 (1.024-01.196)), hippocampal size 0.831 (0.702-0.948)). study provides notable advancement existing literature offering genetic evidence underscores therapeutic advantages focusing on gene treatment insight not only contributes understanding but guides future discovery efforts.

Язык: Английский

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Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Дек. 12, 2023

Abstract Extracellular vesicles (EVs) released by human induced pluripotent stem cell-derived neural cells (hiPSC-NSCs) are enriched with miRNAs and proteins capable of mediating robust antiinflammatory activity. The lack tumorigenic immunogenic properties ability to permeate the entire brain incorporate into microglia following intranasal (IN) administrations makes them an attractive biologic for curtailing chronic neuroinflammation in neurodegenerative disorders. We tested hypothesis that IN hiPSC-NSC-EVs can alleviate cognitive impairments peripheral lipopolysaccharide (LPS) challenge. Adult male, C57BL/6J mice received intraperitoneal injections LPS (0.75 mg/kg) seven consecutive days. Then, either vehicle (VEH) or (~ 10 × 9 EVs/administration, thrice over 6 days). A month later, all groups were investigated function behavioral tests euthanized histological biochemical studies. Mice receiving VEH after displayed deficits associative recognition memory, temporal pattern processing, separation. Such associated increased incidence activated presenting NOD-, LRR-, pyrin domain containing 3 (NLRP3) inflammasomes, elevated levels NLRP3 inflammasome mediators end products, decreased neurogenesis hippocampus. In contrast, various measures closer naive mice. Significantly, these diminished microglial activation, proinflammatory cytokines, a level matching age-matched naïve controls. Thus, efficacious approach reducing neuroinflammation-induced impairments.

Язык: Английский

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