Misfolded α-Synuclein in Autosomal Dominant Alzheimer's Disease.

We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer's disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD.

MOG Antibodies Restricted to CSF in Children With Inflammatory CNS Disorders.

OBJECTIVES: To assess the clinical significance of myelin oligodendrocyte glycoprotein antibodies (MOG-abs) restricted to CSF in children with inflammatory CNS disorders. METHODS: Patients included 760 children (younger than 18 years) from 3 multicenter prospective cohort studies: (A) acquired demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM); (B) non-ADEM encephalitis; and (C) noninflammatory neurologic disorders. For all cases, paired serum/CSF samples were systematically examined using brain immunohistochemistry and live cell-based assays. RESULTS: A total of 109 patients (14%) had MOG-abs in serum or CSF: 79 from cohort A, 30 from B, and none from C. Of these, 63 (58%) had antibodies in both samples, 37 (34%) only in serum, and 9 (8%) only in CSF. Children with MOG-abs only in CSF were older than those with MOG-abs only in serum or in both samples (median 12 vs 6 vs 5 years, p = 0.0002) and were more likely to have CSF oligoclonal bands (86% vs 12% vs 7%, p = 0.0001) and be diagnosed with multiple sclerosis (6/9 [67%] vs 0/37 [0%] vs 1/63 [2%], p < 0.0001). DISCUSSION: Detection of MOG-abs in serum or CSF is associated with CNS inflammatory disorders. Children with MOG-abs restricted to CSF are more likely to have CSF oligoclonal bands and multiple sclerosis than those with MOG-abs detectable in serum.

Impact of demographics and comorbid conditions on plasma biomarkers concentrations and their diagnostic accuracy in a memory clinic cohort.

Plasma biomarkers have emerged as promising tools for identifying amyloid beta (Aß) pathology. Before implementation in routine clinical practice, confounding factors modifying their concentration beyond neurodegenerative diseases should be identified. We studied the association of a comprehensive list of demographics, comorbidities, medication and laboratory parameters with plasma p-tau181, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) on a prospective memory clinic cohort and studied their impact on diagnostic accuracy for discriminating CSF/amyloid PET-defined Aß status. Three hundred sixty patients (mean age 66.5 years, 55% females, 53% Aß positive) were included. Sex, age and Aß status-adjusted models showed that only estimated glomerular filtration rate (eGFR, standardized ß -0.115 [-0.192 to -0.035], p = 0.005) was associated with p-tau181 levels, although with a much smaller effect than Aß status (0.685 [0.607-0.763], p < 0.001). Age, sex, body mass index (BMI), Charlson comorbidity index (CCI) and eGFR significantly modified GFAP concentration. Age, blood volume (BV) and eGFR were associated with NfL levels. p-tau181 predicted Aß status with 87% sensitivity and specificity with no relevant increase in diagnostic performance by adding any of the confounding factors. Using two cut-offs, plasma p-tau181 could have spared 62% of amyloid-PET/CSF testing. Excluding patients with chronic kidney disease did not change the proposed cut-offs nor the diagnostic performance. In conclusion, in a memory clinic cohort, age, sex, eGFR, BMI, BV and CCI slightly modified plasma p-tau181, GFAP and NfL concentrations but their impact on the diagnostic accuracy of plasma biomarkers for Aß status discrimination was minimal.

Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome.

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.