CSF synaptic biomarkers and cognitive impairment in multiple sclerosis.

Background: People with multiple sclerosis (PwMS) experience various degrees of cognitive impairment (CI). Synaptic dysfunction may contribute to CI in PwMS but cerebrospinal fluid (CSF) synaptic biomarkers are unexplored in MS.

Objective: To assess the role of CSF synaptosomal-associated protein 25 (SNAP-25), β-synuclein, neurogranin and neurofilament light chain protein (NfL) in patients with early relapsing MS with and without CI.

Research advancement in fluid biomarkers for Parkinson's disease.

Introduction: Diagnostic criteria for Parkinson's disease (PD) rely on clinical, mainly motor, features, implying that pre-motor phase cannot be accurately identified. To achieve a reliable early diagnosis, similar to what has been done for Alzheimer's disease (AD), a shift from clinical to biological identification of PD is being pursued. This shift has taken great advantage from the research on cerebrospinal fluid (CSF) biomarkers as they mirror the ongoing molecular pathogenic mechanisms taking place in PD, thus intercepting the disease timely with respect to clinical manifestations.

CSF neurosecretory proteins VGF and neuroserpin in patients with Alzheimer's and Lewy body diseases.

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.

Fully automated measurement of plasma Aβ42/40 and p-tau181: Analytical robustness and concordance with cerebrospinal fluid profile along the Alzheimer's disease continuum in two independent cohorts.

Introduction: For routine clinical implementation of Alzheimer's disease (AD) plasma biomarkers, fully automated random-access platforms are crucial to ensure reproducible measurements. We aimed to perform an analytical validation and to establish cutoffs for AD plasma biomarkers measured with Lumipulse.

Methods: Two cohorts were included.

Investigating alpha-synuclein co-pathology in Alzheimer's disease by means of cerebrospinal fluid alpha-synuclein seed amplification assay.

Introduction: Lewy body disease, a frequently observed co-pathology in Alzheimer's disease (AD), can be identified antemortem in cerebrospinal fluid (CSF) by α-synuclein seed amplification assay (αS-SAA). The prevalence and clinical impact of CSF αS-SAA positivity in AD are still unknown.

Methods: αS-SAA was performed on CSF samples from 240 AD patients (preclinical, prodromal, and dementia stages), 85 controls, 84 patients with Parkinson's disease (PD), and 21 patients with PD with dementia or dementia with Lewy bodies.

The Immune Signature of CSF in Multiple Sclerosis with and without Oligoclonal Bands: A Machine Learning Approach to Proximity Extension Assay Analysis.

Early diagnosis of multiple sclerosis (MS) relies on clinical evaluation, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis. Reliable biomarkers are needed to differentiate MS from other neurological conditions and to define the underlying pathogenesis. This study aimed to comprehensively profile immune activation biomarkers in the CSF of individuals with MS and explore distinct signatures between MS with and without oligoclonal bands (OCB).

Trajectories of CSF and plasma biomarkers across Alzheimer's disease continuum: disease staging by NF-L, p-tau181, and GFAP.

CSF-to-plasma transition will open new avenues for molecular phenotyping of Alzheimer's disease (AD). Here we evaluated a panel of AD biomarkers in matched CSF and plasma samples across the AD continuum, from preclinical AD to dementia. The aims were to: 1) compare diagnostic performance of the two biofluids, 2) evaluate trajectories of the biomarkers along AD progression.

Required improvements for cerebrospinal fluid-based biomarker tests of Alzheimer's disease.

Introduction: Cerebrospinal fluid (CSF) biomarkers represent a well-established tool for diagnosing Alzheimer's disease (AD), independently from the clinical stage, by reflecting the presence of brain amyloidosis (A+) and tauopathy (T+). In front of this important achievement, so far, (i) CSF AD biomarkers have not yet been adopted for routine clinical use in all Centers dedicated to AD, mainly due to inter-lab variation and lack of internationally accepted cutoff values; (ii) we do need to add other biomarkers more suitable to correlate with the clinical stage and disease monitoring; (iii) we also need to detect the co-presence of other 'non-AD' pathologies.

Areas Covered: Efforts to establish standardized cutoff values based on large-scale multi-center studies are discussed.

CSF and plasma Aβ42/40 across Alzheimer's disease continuum: comparison of two ultrasensitive Simoa assays targeting distinct amyloid regions.

Objectives: Decreased cerebrospinal fluid (CSF) amyloid beta 42/40 ratio (Aβ42/40) is one of the core Alzheimer's disease (AD) biomarkers. Measurement of Aβ42/40 in plasma has also been proposed as a surrogate marker for amyloidosis, however the validity and the diagnostic performance of this biomarker is still uncertain. Here we evaluated two immunoassays targeting distinct regions of the amyloid peptides by (a) performing a method comparison in both CSF and plasma, and (b) assessing the diagnostic performance across the AD continuum.

Potential diagnostic value of CSF metabolism-related proteins across the Alzheimer's disease continuum.

Background: Alzheimer's disease (AD) cerebrospinal fluid (CSF) core biomarkers (Aβ42/40 ratio, p-tau, and t-tau) provide high diagnostic accuracy, even at the earliest stage of disease. However, these markers do not fully reflect the complex AD pathophysiology. Recent large scale CSF proteomic studies revealed several new AD candidate biomarkers related to metabolic pathways.

CSF Synaptic Biomarkers in AT(N)-Based Subgroups of Lewy Body Disease.

Background And Objectives: Patients with Lewy body disease (LBD) often show a co-occurring Alzheimer disease (AD) pathology. CSF biomarkers allow the detection in vivo of AD-related pathologic hallmarks included in the amyloid-tau-neurodegeneration (AT(N)) classification system. Here, we aimed to investigate whether CSF biomarkers of synaptic and neuroaxonal damage are correlated with the presence of AD copathology in LBD and can be useful to differentiate patients with LBD with different AT(N) profiles.

CSF neurochemical profile and cognitive changes in Parkinson's disease with mild cognitive impairment.

Pathophysiological substrate(s) and progression of Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) are still matter of debate. Baseline cerebrospinal fluid (CSF) neurochemical profile and cognitive changes after 2 years were investigated in a retrospective series of PD-MCI (n = 48), cognitively normal PD (PD-CN, n = 40), prodromal Alzheimer's disease (MCI-AD, n = 25) and cognitively healthy individuals with other neurological diseases (OND, n = 44). CSF biomarkers reflecting amyloidosis (Aβ42/40 ratio, sAPPα, sAPPβ), tauopathy (p-tau), neurodegeneration (t-tau, NfL, p-NfH), synaptic damage (α-syn, neurogranin) and glial activation (sTREM2, YKL-40) were measured.

LRRK2 Quantification in Cerebrospinal Fluid of Patients with Parkinson's Disease and Atypical Parkinsonian Syndromes.

Background: The alteration of leucine-rich repeat kinase 2 (LRRK2) kinase activity is thought to be involved in Parkinson's disease (PD) pathogenesis beyond familiar cases, and LRRK2 inhibitors are currently under investigation. Preliminary data suggest a relationship between LRRK2 alteration and cognitive impairment in PD.

Objective: To investigate cerebrospinal fluid (CSF) LRRK2 levels in PD and other parkinsonian disorders, also correlating them with cognitive impairment.

Psychiatric symptoms in multiple sclerosis: a biological perspective on synaptic and network dysfunction.

Psychiatric symptoms frequently occur in multiple sclerosis (MS), presenting with a complex phenomenology that encompasses a large clinical spectrum from clear-cut psychiatric disorders up to isolated psychopathological manifestations. Despite their relevant impact on the overall disease burden, such clinical features are often misdiagnosed, receive suboptimal treatment and are not systematically evaluated in the quantification of disease activity. The development of psychiatric symptoms in MS underpins a complex pathogenesis involving both emotional reactions to a disabling disease and structural multifocal central nervous system damage.

Clinical correlates of state and trait anxiety in multiple sclerosis.

Background: Anxiety represents one of the most prevalent psychiatric symptoms in multiple sclerosis (MS), impacting the overall disease burden and quality of life. This psychopathological feature can be expressed as state (S-ANX) and trait (T-ANX) anxiety, but few studies specifically evaluated these two components in MS. The present study was aimed at investigating the prevalence and specific correlates of S-ANX and T-ANX in a cohort of people with MS (PwMS).