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Aggregation-dependent epitope sequence and modification fingerprints of anti-Aβ antibodies

1 week 5 days ago
A hallmark of Alzheimer's disease (AD), the most common form of dementia, is the progressive accumulation of amyloid-beta (Aβ) peptides across distinct brain regions. Anti-Aβ antibodies (Aβ-Abs) targeting specific Aβ variants are essential tools for AD research, diagnostics, and therapy. The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding...
Ivan Talucci

Kidney function and all-cause mortality in the oldest-old population: a three-cohort longitudinal study

1 week 5 days ago
With increasing global life expectancy, the prognostic significance of kidney function in centenarians and supercentenarians should be clarified. The conventional estimated glomerular filtration rate (eGFR) threshold of < 60 mL/min/1.73 m² may not accurately reflect chronic kidney disease (CKD) in this population, highlighting the need for age-adapted definitions. This study investigated the association of kidney function with all-cause mortality across three age groups. Data from the Tokyo...
Hideaki Kurata

NAD+ supplementation for anti-aging and wellness: a PRISMA-guided systematic review of preclinical and clinical evidence

1 week 6 days ago
Nicotinamide adenine dinucleotide (NAD⁺) declines with age, motivating "NAD⁺-boosting" strategies ranging from lifestyle interventions to supplementation with NAD⁺ precursors (e.g., nicotinamide riboside [NR], nicotinamide mononucleotide [NMN]) and, in some wellness settings, parenteral NAD⁺ administration. We conducted a PRISMA-guided systematic review of peer-reviewed human and rodent intervention studies (January 2010-October 2025) evaluating NAD-related compounds administered orally or...
Cory Gallagher

From ageing clocks to organ networks: Biological age-driven organ asynchrony and inter-organ interactions shaping mortality risk

1 week 6 days ago
Ageing is a multidimensional and heterogeneous process that progresses asynchronously across organ systems. Advances in multi-omics technologies have led to the development of diverse ageing clocks, including epigenetic, proteomic, metabolomic, and imaging-based models, which extend beyond estimating crude biological age to more precisely capture organ-specific ageing trajectories and predict age-related diseases and mortality risk. Population-scale studies demonstrate substantial...
Zhenyu Li

Golgi fragmentation driven by the USP11-ITCH axis triggers autolysosomal failure in neurodegeneration

1 week 6 days ago
Golgi fragmentation is a prominent early hallmark of neurodegenerative diseases such as Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS), yet the shared molecular mechanisms underlying this phenomenon remain poorly understood. Here we identify the E3 ubiquitin ligase ITCH as a central regulator of Golgi integrity and proteostasis. Elevated ITCH disrupts both cis- and trans-Golgi networks, dislocates lysosomal hydrolase sorting factors, and impairs maturation of hydrolases. The...
Qiwang Xiang

Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth-Associated Proteins

1 week 6 days ago
Centenarians exhibit remarkable longevity and compression of morbidity making them an ideal population for uncovering proteins associated with successful aging. Using proteomics, we characterized the immune and cardiometabolic profiles of centenarians' plasma from the SWISS100 cohort. We identified 583 differentially expressed proteins (DEPs) by centenarians when compared with hospitalized geriatric patients (age 80-90 years) and younger healthy participants (age 30-60 years). We replicated the...
Flavien Delhaes

Overactivation of Cdc42 GTPase Impairs the Cytotoxic Function of NK Cells From Old Individuals Towards Senescent Fibroblasts

1 week 6 days ago
Senescent fibroblasts accumulate in the connective tissue of all organs and promote organ aging and aging-related diseases. The underlying mechanisms for the accumulation of senescent fibroblasts are poorly understood. Natural killer (NK) cells of innate immunity play a critical role in the removal of tissue resident senescent cells. We here show that NK cells from old adults and old mice fail to efficiently remove senescent fibroblasts. This is due to severely reduced perforin and granzyme B...
Albert Kallon Koroma

Neuroimmune dysregulation in Alzheimer's disease: Mechanisms and therapeutic strategies

2 weeks ago
Alzheimer's disease (AD) is a neurodegenerative disorder characterised by progressive memory loss and cognitive decline. With the global population ageing, the prevalence of AD continues to rise, posing a significant public health challenge. Historically, AD research has centred on two hallmark pathological features: β-amyloid (Aβ) deposition and tau protein hyperphosphorylation. However, repeated failures of therapeutic strategies targeting these pathways in clinical trials have prompted a...
Haili He