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Role of complement and complement-targeted therapeutics in neurological diseases
Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains...
Priming of CD8<sup>+</sup> T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration
Alzheimer's disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8^(+) T cells correlating with tau pathology severity. However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear. In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8^(+) T cells into effector cells. We show that tauopathy mice lacking cDC1s or antigen...
Role of complement and complement-targeted therapeutics in neurological diseases
Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains...
A consensus roadmap from the SENESCENCE2030 network towards precision senescence medicine
No abstract
GLP-1 receptor agonism extends median lifespan in mice
No abstract
Super-precise optical clocks in four nations tick in harmony
Body parts used for ancient Egyptian artworks traced to surprising source
Bats carry dangerous viruses without getting sick. This may be why
Scientists discovered that more than 500 species of vesper bats possess two separate sets of antibody genes, an immune arrangement never before found in mammals. The surprising system could help explain how bats tolerate so many viruses without becoming seriously ill.
New ‘connectome’ shows all 124 million contact points in the fruit fly’s nervous system
Studies cap 20-year project to map an insect’s entire nervous system—and understand how it works
One immune switch may help drive aging across the body
Aging may be partly fueled by immune cells losing their ability to clear away damaged, inflammation-promoting cells. Blocking a single receptor restored that cleanup process in mice, reducing inflammation and helping their organs, muscles, and memory remain remarkably youthful.
Diagnostic performance of plasma pTau217 in genetically admixed South American populations
Plasma pTau217 is a leading biomarker for Alzheimer's disease, but evidence from genetically admixed populations in low- and middle-income countries remains limited. We evaluated the diagnostic performance of pTau217 and pTau217/Aβ42 measured using Simoa technology in memory-clinic cohorts from Brazil (Cog-Aging-Study, n = 353) and Argentina (GeNED.ar, n = 134). Here we show that both biomarkers accurately identified cerebrospinal fluid (CSF)-defined amyloid pathology in Cog-Aging-Study-Brazil...
Dilute electrolytes for suppressing metal anode corrosion during calendar aging and cycling in aqueous zinc batteries
While numerous improvements in cycling stability have been demonstrated for next-generation battery chemistries with metallic anodes, their calendar aging (e.g., capacity loss during idle periods of rest) performance painfully lags behind and remains a critical bottleneck hindering their practical deployment. In contrast to their commercial counterparts, metallic anodes exhibit substantial capacity loss during calendar aging. Despite several recent studies exploring the underlying reasons for...
Longer-lived mammals exhibit greater evolutionary conservatism and epigenetic modification at cancer-associated loci
Peto's paradox underscores the puzzling disconnect between organismal lifespan, body size, and cancer incidence. Here, we investigate this relationship by examining the evolutionary rates of human cancer-associated sites across 58 mammalian species. While overall evolutionary rates at cancer-associated loci do not differ significantly between long-lived and short-lived species, cancer-associated sites show greater evolutionary conservation relative to non-cancer sites within long-lived mammals...
Diagnostic performance of plasma pTau217 in genetically admixed South American populations
Plasma pTau217 is a leading biomarker for Alzheimer's disease, but evidence from genetically admixed populations in low- and middle-income countries remains limited. We evaluated the diagnostic performance of pTau217 and pTau217/Aβ42 measured using Simoa technology in memory-clinic cohorts from Brazil (Cog-Aging-Study, n = 353) and Argentina (GeNED.ar, n = 134). Here we show that both biomarkers accurately identified cerebrospinal fluid (CSF)-defined amyloid pathology in Cog-Aging-Study-Brazil...
Redox-dependent synaptic clustering of gephyrin
Reactive oxygen species (ROS) have been demonstrated to play central functions as signaling molecules thus extending their role beyond oxidative stress in disease and aging. At inhibitory synapses the scaffolding protein gephyrin clusters glycine and GABA type A receptors. Postsynaptic gephyrin clustering is regulated by post-translational modifications such as phosphorylation, S-palmitoylation, and S-nitrosylation, which all critically impact its scaffolding function. Here, we show that...
Natural history and clinical impact of epilepsy in adults with Down syndrome: a multicentre clinical study
BACKGROUND: As individuals with Down syndrome age, they face high risks of Alzheimer's disease and epilepsy. With symptomatic Alzheimer's disease, late-onset myoclonic epilepsy in Down syndrome (LOMEDS) often emerges. We aimed to examine how epilepsy develops in Down syndrome, its timing relative to Alzheimer's disease symptom onset, and its effect on prognosis.
Late-onset seizures as a sentinel of Alzheimer's disease progression in Down syndrome
No abstract
Home- and Community-Based Services Use Is Not Associated With Lower Elder Abuse Likelihood
CONCLUSIONS AND IMPLICATIONS: These findings suggest that HCBS as an aggregate service category is not associated with reduced elder abuse. Future research is needed to examine the role of individual services in elder abuse prevention.
Elderly Health Check-Up and Functional Disability or Death in Adults 75 to 84 Years: A Target Trial Emulation
CONCLUSIONS AND IMPLICATIONS: The evidence is uncertain about the effect of initial EHC participation on the 5-year risk of functional disability or death; the point estimate is compatible with a modest benefit, but the 95% CI included the null. These findings neither support expansion nor justify discontinuation of the EHC program for preventing entry into LTC, and call for replication in additional cohorts before policy changes are considered.
Choose Home: Initial Evaluation of a Novel Home-Based Care Program After Subacute Rehabilitation
Many older adults prefer aging in place, but complex medical and social care needs and fragmented care systems are barriers to maintaining independence at home. Choose Home was implemented at the Veteran Affairs Boston Health Care System in September 2023 to address a critical care gap for patients who seek to remain independent at home but are at high risk for acute care hospitalizations and institutionalization in long-term care facilities. This report describes a subpopulation (n = 16) of...