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Large-scale proteomic analyses of incident Parkinson's disease reveal new pathophysiological insights and potential biomarkers

3 months 1 week ago
The early pathophysiology of Parkinson's disease (PD) is poorly understood. We analyzed 2,920 Olink-measured plasma proteins in 51,804 UK Biobank participants, identifying 859 incident PD cases after 14.45 years. We found 38 PD-related proteins, with six of the top ten validated in the Parkinson's Progression Markers Initiative (PPMI) cohort. ITGAV, HNMT and ITGAM showed consistent significant association (hazard ratio: 0.11-0.57, P = 6.90 × 10^(-24) to 2.10 × 10^(-11)). Lipid metabolism...
Yi-Han Gan

Stressed microglia turn to the dark side in Alzheimer's disease

3 months 1 week ago
A microglia subpopulation termed "dark microglia" has been associated with aging and neurodegeneration, although its role has remained elusive. New research from Flury et al. in this issue of Neuron shows that dark microglia drive neurodegeneration via secretion of toxic lipids.¹.
Gilbert Di Paolo

Can a novel set of handgrips on a walking frame increase stability and support users when transferring to/from a chair?

3 months 1 week ago
INTRODUCTION: One important aspect of walking aid use is transferring safely to the aid from sitting and transferring back to the chair after walking, since these activities have been associated with falls in older adults. Standard frames require their user to push off the chair or ask for help from a carer, which may over time lead to back pain. This study's aim was to assess whether novel handgrips located above the rear feet of a walking frame would facilitate safe transfer as compared to...
Sibylle Brunhilde Thies

Activity-based sensing reveals elevated labile copper promotes liver aging via hepatic ALDH1A1 depletion

3 months 1 week ago
Oxidative stress plays a key role in aging and related diseases, including neurodegeneration, cancer, and organ failure. Copper (Cu), a redox-active metal ion, generates reactive oxygen species (ROS), and its dysregulation contributes to aging. Here, we develop activity-based imaging probes for the sensitive detection of Cu(I) and show that labile hepatic Cu activity increases with age, paralleling a decline in ALDH1A1 activity, a protective hepatic enzyme. We also observe an age-related...
Zhenxiang Zhao

Neuronal FAM171A2 mediates alpha-synuclein fibril uptake and drives Parkinson's disease

3 months 1 week ago
Neuronal accumulation and spread of pathological α-synuclein (α-syn) fibrils are key events in Parkinson's disease (PD) pathophysiology. However, the neuronal mechanisms underlying the uptake of α-syn fibrils remain unclear. In this work, we identified FAM171A2 as a PD risk gene that affects α-syn aggregation. Overexpressing FAM171A2 promotes α-syn fibril endocytosis and exacerbates the spread and neurotoxicity of α-syn pathology. Neuronal-specific knockdown of FAM171A2 expression shows...
Kai-Min Wu

Temporal autocorrelation is predictive of age-An extensive MEG time-series analysis

3 months 1 week ago
Understanding the evolving dynamics of the brain throughout life is pivotal for anticipating and evaluating individual health. While previous research has described age effects on spectral properties of neural signals, it remains unclear which ones are most indicative of age-related processes. This study addresses this gap by analyzing resting-state data obtained from magnetoencephalography (MEG) in 350 adults (18 to 88 y). We employed advanced time-series analysis at the brain region level and...
Christina Stier

Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain

3 months 1 week ago
Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes...
Heejong Kim

Metabolomic insight into the link of intermuscular fat with cognitive performance: the Health ABC Study

3 months 1 week ago
There is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging, and Body Composition...
Richard Xu

Transcriptomic profiling of senescence effects on blood-brain barrier-related gene expression in brain capillary endothelial cells in a mouse model of paclitaxel-induced chemobrain

3 months 1 week ago
Chemotherapy-induced cognitive impairment (CICI), commonly referred to as "chemobrain," is a frequent and debilitating side effect experienced by cancer survivors treated with paclitaxel (PTX). Preclinical models have shown that PTX promotes cerebromicrovascular endothelial cell senescence, leading to chronic blood-brain barrier (BBB) disruption and neuroinflammation. Conversely, the elimination of senescent cells through senolytic therapies has been shown to restore BBB integrity, reduce...
Roland Patai

Cisplatin and methotrexate induce brain microvascular endothelial and microglial senescence in mouse models of chemotherapy-associated cognitive impairment

3 months 1 week ago
The increasing number of cancer survivors has brought heightened attention to the side effects of cancer therapies, including chemotherapy-related cognitive impairment (CRCI, commonly referred to as "chemobrain"). Cisplatin and methotrexate, commonly used first-line chemotherapeutics in gynecologic oncology for cancers such as breast, ovarian, and bladder cancer, are clinically associated with long-term cognitive deficits. Building on our previous preclinical studies demonstrating that...
Boglarka Csik