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Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease

5 months 2 weeks ago
Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8^(+) cells, CD4^(+) T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive...
Pavle Boskovic

Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease

5 months 2 weeks ago
Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8^(+) cells, CD4^(+) T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive...
Pavle Boskovic

Short-range electrostatic screening in ionic liquids as inferred by direct force measurements

5 months 2 weeks ago
Previous experimental reports of long-range interactions in ionic liquids (ILs) stand in contradiction with theoretical predictions and numerical simulations. To provide insights into the literature discrepancies regarding the experimental ranges of electrostatic screening, claimed with orders of magnitude larger, the interactions between pairs of mica and borosilicate surfaces confining ILs are investigated by two complementary advanced Surface Force Apparatuses. Regardless of differences in...
Benjamin Cross

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

5 months 2 weeks 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

5 months 2 weeks 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

5 months 2 weeks 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

5 months 2 weeks 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

5 months 2 weeks 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