👤 Camille Piguet

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Increasing evidence implicates systemic lipid perturbation in ALS pathogenesis. However, the extent and nature of apolipoprotein changes underlying lipid perturbations in ALS remain largely unknown. To address this, we performed a comprehensive analysis of major apolipoproteins involved in lipid metabolism and examined their association with lipoprotein membrane lipids in sporadic ALS (n = 32) and age-matched healthy controls (n = 32), using ELISA and liquid chromatography-mass spectrometry. Compared with controls, serum levels of apoB, apoCI, apoCII, apoCIII and apoE were significantly elevated in ALS, whereas apoAI and apoAII were unchanged. Distributional analyses demonstrated a relative decrease in apoAI and an increase in apoB in ALS, resulting in an elevated apoB/apoAI ratio, a marker of atherogenic risk, alongside a reduced apoAI/apoE ratio. Correlation analyses revealed strengthened interrelationships among apolipoproteins in ALS, suggesting altered regulatory coordination. At the lipid level, phosphatidylcholine (PC) was increased, whereas sphingomyelin (SM) was reduced in ALS serum. Notably, the strong associations of apoB to both PC and SM observed in controls were absent in ALS. Biomarker analyses identified apoE as the strongest discriminator between ALS and control groups. Collectively, these findings demonstrate a coordinated disruption of apolipoproteins and lipoprotein-associated lipids in ALS serum, with likely functional consequences for lipoprotein metabolism. This study provides new insights into lipid dysregulation in ALS pathobiology and supports the emerging view that ALS encompasses not only neurodegenerative processes but also systemic metabolic reprogramming. Show less

Anxiety is an aggravating comorbidity of many psychiatric disorders that is often underdiagnosed and undertreated, and little is known on the mechanisms underlying its regulation. Here, we find that serum LPA16:0 abundance increases with trait anxiety in both humans and mice; while high LPA16:0 levels are sufficient to reduce the in vitro proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor LPA Show less

Timely diagnosis is crucial for managing neurodegenerative conditions. This study investigated whether time from symptom onset to diagnosis differs by clinical syndrome and sex. This retrospective, cross-sectional study included 591 participants with Alzheimer's disease (AD), frontotemporal dementia (FTD) subtypes (behavioral variant FTD [bvFTD], semantic dementia [SD], and progressive non-fluent aphasia), logopenic progressive aphasia (LPA), and syndromes associated with movement disorders (corticobasal syndrome, FTD with motor neuron disease [FTD-MND], and progressive supranuclear palsy). Bayesian regression models were used to compute diagnostic timelines. Compared to AD (3.35 years; 95% credible interval [CrI]: 3.03-3.72), SD and bvFTD had additional delays of 9.7 (95% CrI: 1.96-20.64) and 14.82 months (95% CrI: 6.94-25.42), respectively, while FTD-MND was shorter by 11.62 months (95% CrI: -15.7 to -4.68). Men with bvFTD had 23.64 month longer delays than women (95% CrI: 10.35-44.33). Diagnostic delays may reflect syndrome-specific clinical features, diagnostic complexity, and sociocultural factors. Findings highlight the need for improved diagnostic pathways and pre-clinical biomarkers to facilitate earlier identification. Bayesian analyses revealed that diagnostic delays differ by syndrome and sex.Alzheimer's disease (AD) was diagnosed on average 3.35 years after symptom onset.Diagnoses were delayed in semantic and behavioral variant frontotemporal dementia (bvFTD) compared to AD.Men with bvFTD had longer delays than women.Findings support need for improved diagnostic pathways and pre-clinical biomarkers. Show less