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Background: VGF and neuroserpin are neurosecretory proteins involved in the pathophysiology of neurodegenerative diseases. We aimed to evaluate their cerebrospinal fluid (CSF) concentrations in patients with Alzheimer's disease (AD) and Lewy body disease (LBD)., Methods: We measured CSF VGF [AQEE] peptide and neuroserpin levels in 108 LBD patients, 76 AD patients and 37 controls, and tested their associations with clinical scores and CSF AD markers., Results: We found decreased CSF levels of VGF [AQEE] in patients with LBD and dementia compared to controls (p = 0.016) and patients with AD-dementia (p = 0.011), but with significant influence of age and sex distribution. Moreover, we observed, on the one hand, a significant associations between lower VGF [AQEE] and neuroserpin levels and poorer cognitive performance (i.e., lower Mini-Mental State Examination scores). On the other hand, higher levels of CSF tau proteins, especially pTau181, were significantly associated with higher concentrations of VGF [AQEE] and neuroserpin. Indeed, LBD patients with AD-like CSF profiles, especially T+ profiles, had higher levels of VGF [AQEE] and neuroserpin compared to controls and LBD/T- cases., Discussion: CSF VGF [AQEE] and neuroserpin may show a complex relationship with cognitive decline when the levels are reduced, and with AD pathology when levels are increased. They may represent novel markers of neurosecretory impairment in neurodegenerative disorders., Competing Interests: Declaration of competing interest PO received consultancy fees from LifeArc. MO gave scientific advice for Fujirebio, Roche, Biogen and Axon. The other authors have nothing to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: For multiple sclerosis (MS) phenotypes classification, the presence of "disease activity" can be defined by clinical relapses and/or by magnetic resonance imaging (MRI) through gadolinium-enhancing (Gd+) lesions or new/enlarged T2 lesions. Recent MRI and pathology findings have demonstrated Gd deposition in the brain, suggesting to avoid Gd administration when dispensable. In this scenario, we aimed to evaluate the contribution of post-contrast MRIs to the definition of "active" MS phenotype., Methods: We retrospectively selected 84 "active" relapsing-remitting MS (RRMS) patients according to Lublin 2013, calculating both the number of Gd+ lesions not detectable as new/unequivocally enlarged on T2 images and the proportion of patients who would be still correctly classified as "active" without Gd administration., Results: 13 out of 164 (7.9%) Gd+ lesions did not correspond to a new/enlarged T2 lesion. Gd administration did not modify the classification of MS as "active" in 83 out of 84 subjects (98.8%)., Conclusion: The contribution of Gd+ lesions to the correct classification of RRMS patients as "active" is marginal, thus limiting the need of routine Gd administration for this scope. Further studies are warranted to support these conclusions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The diagnosis of Alzheimer's disease (AD) relies on the presence of amyloidosis and tauopathy, as reflected in cerebrospinal fluid (CSF), independently from the clinical stage. Recently, CSF d-serine has been proposed as a possible new AD biomarker, reflecting dysfunctional activation of neuronal glutamatergic N-methyl-d-aspartate receptor (NMDAR). In this study, we measured blood serum and CSF concentration of two NMDAR modulators, such as d-serine and d-aspartate, in a cohort of drug-free subjects encompassing the whole AD clinical spectrum. In addition, we also analyzed d-serine levels in a cohort of post-mortem AD and control cortex samples. We reported unaltered serum and CSF concentrations of d-serine and d-aspartate in AD patients both during the AD progression and compared to non-demented controls. Accordingly, no correlation was detected between serum or CSF d-serine content and mini-mental state examination or Clinical Dementia Rating. Similarly, cortical d-serine levels were also unaltered in post-mortem samples of AD patients. Overall, our results failed to confirm previous findings indicating the CSF d-serine as a novel biomarker for AD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An accurate and early diagnosis of degenerative parkinsonian syndromes is a major need for their correct and timely therapeutic management. The current diagnostic criteria are mostly based on clinical features and molecular imaging. However, diagnostic doubts often persist especially in the early stages of diseases when signs are slight, ambiguous and overlapping among different syndromes. Molecular imaging may not be altered in the early stages of diseases, also failing to discriminate among different syndromes. Cerebrospinal fluid (CSF) represents an ideal source of biomarkers reflecting different pathways of neuropathological changes taking place in the brain and preceding the clinical onset. The aim of this review is to provide un update on CSF biomarkers in parkinsonian disorders, discussing in detail their association with neuropathological correlates. Their potential contribution in differential diagnosis and prognostic assessment of different parkinsonian syndromes is also discussed. Before entering the clinical use both for diagnostic and prognostic purposes, these CSF biomarkers need to be thoroughly assessed in terms of pre-analytical and analytical variability, as well as to clinical validation in independent cohorts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Multiple sclerosis (MS) usually presents at onset with a clinically isolated syndrome (CIS). According to 2010 McDonald criteria, a diagnosis of MS can be made if CIS patients satisfy clinical/MRI criteria of both dissemination in time (DIT) and space (DIS)., Objective: The aim of this study was to analyze the follow-up data and possible prognostic factors of CIS patients satisfying DIS MRI criteria., Patients and Methods: We performed a retrospective, multicenter study across 2 Italian centers. Clinical, MRI, and laboratory assessments were performed according to real-life clinical workup., Results: Out of the 137 enrolled patients, during a median follow-up time of 3.1years, 116 (84.7%) converted to MS with the large majority (78.4%) of the converters developing MS within 1year. In multivariate analysis, baseline predictors of an earlier conversion were a cerebellar/brainstem CIS (HR 2.00, 95% CI: 1.3-3.0, p=0.001) and the presence of all the Barkhof-Tintore MRI criteria (HR 1.67, 95% CI: 1.1-2.6, p=0.028)., Conclusions: Patients with CIS and DIS are at very high risk of an early conversion to MS. The onset with cerebellar/brainstem symptoms and the evidence of a higher MRI lesion load at baseline are the strongest independent predictors of an early conversion to MS., (Copyright © 2017 Elsevier B.V. All rights reserved.)