Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology.

Introduction: Semorinemab, an anti-tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action.

Methods: Qualified assays were used to measure biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participant samples in Tauriel (NCT03289143) and Lauriet (NCT03828747) Phase II trials.

Large-scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease.

Introduction: A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest.

Methods: We conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation.

Results: We identified 61 proteins significantly associated with the AT category (P < 5.

Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex.

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS.

Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation.

Background: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available.

Objective: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation.

Methods: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models.

Prepandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults.

Background And Objectives: Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer disease (AD), which may accelerate disease progression. We investigated whether β-amyloid, cortical thickness in medial temporal lobe structures, neuroinflammation, and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement.

Methods: This retrospective observational study included cognitively unimpaired older adults from the Alzheimer's and Families cohort, the majority with a family history of sporadic AD.

Aetiologies and factors associated with poor clinical outcomes in rhabdomyolysis: a retrospective cohort study in an Australian trauma centre.

Rhabdomyolysis is a clinical syndrome with significant morbidity and mortality that occurs as a result of traumatic and non-traumatic aetiologies. Acute kidney injury, the need for dialysis, and death, can occur due to rhabdomyolysis. This study explores the aetiologies, clinical outcomes and associated factors for poor outcomes in a cohort of patients with rhabdomyolysis in a tertiary trauma centre in Australia.