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Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis

1 month 2 weeks ago
Elevated blood levels of phosphorylated tau (p-tau) are diagnostic of Alzheimer disease and are associated with the deposition of amyloid-β in the cerebral neuropil. Elevated p-tau levels have also been associated with cerebral deposition of Danish amyloid and prion protein amyloid. Here we analyzed p-tau in serum from four different cohorts of people with the most common types of systemic amyloidosis, transthyretin (ATTR) amyloidosis and immunoglobulin light chain (AL) amyloidosis. We found...
Stephan A Kaeser

Microglia protein profiles in CSF across Alzheimer's disease clinical stages

1 month 2 weeks ago
Microglia are implicated in the progression of Alzheimer's disease (AD) pathology from its earliest stages, suggesting that cerebrospinal fluid (CSF) microglia profiling across clinical AD stages can aid in treatment development and monitoring. We analyzed two CSF cohorts (n = 834) that span from unimpaired controls to preclinical and dementia AD stages, identifying 109 dysregulated microglia-related proteins. Enrichment analyses revealed innate immune processes and cellular recruitment in...
Elena-Raluca Blujdea

Stroke in persistent chronic kidney disease condition alters innate-immunity to escalate mitochondrial dysfunction and aging

1 month 2 weeks ago
Stroke is one of the leading causes of mortality and disability worldwide, with ischemic stroke accounting for over 87% of all stroke cases. Chronic kidney disease (CKD) is one of the major risk factors for stroke, as CKD patients have shown evidence of impaired cerebral autoregulation leading to exacerbated stroke pathology. The worsening of stroke outcomes in CKD patients is limitedly understood. Inflammation plays a pivotal role in driving the CKD-stroke pathology. The cGAS-STING (cyclic...
Aishika Datta

Intrinsic capacity and stroke risk in a multiple cohort study

1 month 2 weeks ago
Intrinsic capacity is a concept established by the World Health Organization (WHO). The concept aims to represent the total of a person's physical and mental abilities, measured across five domains: cognition, psychological, sensory, vitality, and locomotor that were identified as crucial for healthy aging. The aim being to shift focus from disease to function to predict health, disability, and frailty. In this large-scale cohort study, we aim to investigate the association between intrinsic...
Ying Li

Intestinal interoceptive dysfunction drives age-associated cognitive decline

1 month 2 weeks ago
Ageing is accompanied by declining memory function, with extremely heterogeneous manifestation in the human population¹. Brain-extrinsic factors influencing cognitive decline, such as gastrointestinal signals, have emerged as attractive targets for peripheral interventions^(2-6), but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which...
Timothy O Cox

Ageing promotes metastasis via activation of the integrated stress response

1 month 2 weeks ago
Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood¹. Here we show that ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic dissemination through epigenetic activation of the integrated stress response (ISR). The ISR effector ATF4 drives epithelial and metabolic plasticity, conferring metastatic competence. Mechanistically,...
Angana A H Patel