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A genetically encoded selection for amyloid-β oligomer binders

1 week 1 day ago
Soluble amyloid-β oligomers (AβOs) are a hypothesized source of neurotoxicity in Alzheimer disease. Binding proteins that recognize these species may have high utility in diagnostic and therapeutic applications. However, identifying binders to AβOs directly generated from the aggregation cascade is challenging because of the short lifetime and low concentrations of oligomer populations. We report a strategy to detect binding to AβOs formed during Aβ42 aggregation using a genetically encoded...
ByungUk Lee

The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging

1 week 1 day ago
More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions....
Farhad Imam

APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases

1 week 1 day ago
The APOE ε4 genetic variant is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is increasingly being implicated in other neurodegenerative diseases. Using the Global Neurodegeneration Proteomics Consortium SomaScan dataset covering 1,346 cerebrospinal fluid (CSF) and 9,924 plasma samples, we used machine learning-based proteome profiling to identify an APOE ε4 proteomic signature shared across individuals with AD, frontotemporal dementia (FTD), Parkinson's disease...
Artur Shvetcov

Shared and disease-specific pathways in frontotemporal dementia and Alzheimer's and Parkinson's diseases

1 week 1 day ago
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and frontotemporal dementia (FTD), exhibit distinct yet overlapping pathological mechanisms. Leveraging large-scale plasma proteomics data from the Global Neurodegeneration Proteomics Consortium, we analyzed 10,527 plasma samples (1,936 AD, 525 PD, 163 FTD, 1,638 dementia and 6,265 controls) to identify disease-specific and shared proteins across NDs. We identified 5,187 proteins significantly associated...
Muhammad Ali

Time is encoded by methylation changes at clustered CpG sites

1 week 1 day ago
Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent methylation changes occur regionally across clusters of CpG sites either stochastically or in a coordinated block-like manner. Deep learning of single-molecule patterns from two genomic loci predicts chronological age with a median accuracy of 1.36-1.7 years...
Bracha-Lea Ochana

Killing wisely: precision senolytics in the age of frailty

1 week 1 day ago
Cellular senescence plays a dual role in tissue biology by promoting tumor suppression and wound healing when transient but driving inflammation, fibrosis, and age-related disease when persistent. The growing recognition that senescent cell clearance can reverse these pathologies has catalyzed efforts to develop therapeutics that preferentially kill senescent cells (also known as "senolytics"). However, clinical translation from bench to bedside remains challenging due to senescent state...
Valentin J A Barthet

Scaling life as an interspecies hallmark of aging

1 week 1 day ago
Across species, the "pace of life"-encompassing development, reproduction, and senescence-varies widely, yet the molecular mechanisms that regulate these interspecies trajectories of aging remain elusive. Even among vertebrates, a 1000-fold difference in life span is observed between species, ranging from several months in the turquoise killifish to half a millennium in the Greenland shark. As a relatively "young" area of investigation, aging research lacks the unifying conceptual frameworks...
Itamar Harel

Activated GDF11/8 subforms predict cardiovascular events and mortality in humans

1 week 1 day ago
Circulating Growth Differentiation Factors 11 and 8 (GDF11/8) exist in both latent and active forms, and it is unclear if specific forms can predict disease outcomes. Our data suggest that a dual-specific aptamer selectively binds GDF11/8 after prodomain activation. In 11,609 patients at risk for future cardiovascular events, low dual-specific aptamer-detected GDF11/8 levels strongly predicted adverse outcomes, including cardiovascular events (HR = 0.43, p = 9.1 × 10⁻⁶³) and all-cause mortality...
Ryan G Walker

Sirtuins and their role in ovarian aging-related fibrosis predisposing to ovarian cancer

1 week 1 day ago
The pursuit of understanding early genetic or protein markers for ovarian aging has garnered considerable attention in the realm of reproductive medicine. Sirtuins (SIRTs) are a group of proteins that are NAD^(+)-dependent, and thanks to their properties, they are able to change the acetylation profile of proteins and post-translationally modify their functions, too. Previous research provided evidence that SIRTs influence fibrosis levels in several organs. With regard to ovaries, fibrosis is...
Arkadiusz Grzeczka