Myelin basic protein and TREM2 quantification in the CSF of patients with Multiple System Atrophy and other Parkinsonian conditions.

Background: It is well known that myelin disruption and neuroinflammation are early and distinct pathological hallmarks in multiple system atrophy (MSA) as well as in idiopathic Parkinson's disease and in other atypical Parkinsonian syndromes. The objective of this study was to assess the value of non-neuronal biomarker candidates that reflect myelin disruption and neuroinflammation.

Methods: Myelin basic protein (MBP) and the soluble form of TREM2 were quantified in a comprehensive movement disorder cohort from two different neurological centers, comprising a total of 171 CSF samples.

Regulated Proteolysis Induces Aberrant Phase Transition of Biomolecular Condensates into Aggregates: A Protective Role for the Chaperone Clusterin.

Several proteins associated with neurodegenerative diseases, such as the mammalian prion protein (PrP), undergo liquid-liquid phase separation (LLPS), which led to the hypothesis that condensates represent precursors in the formation of neurotoxic protein aggregates. However, the mechanisms that trigger aberrant phase separation are incompletely understood. In prion diseases, protease-resistant and infectious amyloid fibrils are composed of N-terminally truncated PrP, termed C2-PrP.

Risk factors and clinical significance of post-stroke incident ischemic lesions.

Introduction: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.

Methods: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months.

Results: At 6 months, 78 patients (15.

Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo.

Introduction: Cellular prion protein (PrP) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear.

Methods: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrP-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest.

Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.

Proteolytic cell surface release ('shedding') of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, for the human body neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated thus far.

SIMOA Diagnostics on Alzheimer's Disease and Frontotemporal Dementia.

Background: Accurate diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic-clinical characteristics.

Methods: 136 subjects (AD: = 43, FTD: = 33, Controls: = 60) participated.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

A Comparison of RML Prion Inactivation Efficiency by Heterogeneous and Homogeneous Photocatalysis.

Prions are proteinaceous pathogens responsible for a variety of devastating diseases in mammals, including scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease (CJD) in humans. They are characterized by their exceptional persistence to common inactivation procedures. This applies to all possible sources of prion contamination as prions may be present in the tissues and biological fluids of infected individuals.

Unmet needs of biochemical biomarkers for human prion diseases.

Although the development of aggregation assays has noticeably improved the accuracy of the clinical diagnosis of prion diseases, research on biomarkers remains vital. The major challenges to overcome are non-invasive sampling and the exploration of new biomarkers that may predict the onset or reflect disease progression. This will become extremely important in the near future, when new therapeutics are clinically evaluated and eventually become available for treatment.

Αnti-prion effects of anthocyanins.

Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrP, into the pathogenic isoform, PrP. Prion diseases are invariably fatal and despite ongoing research, no effective prophylactic or therapeutic avenues are currently available.

[Clinical characteristics and diagnostics of human spongiform encephalopathies: an update].

Human spongiform encephalopathies are rare transmissible neurodegenerative diseases of the brain and the nervous system that are caused by misfolding of the physiological prion protein into a pathological form and its deposition in the central nervous system (CNS). Prion diseases include Creutzfeldt-Jakob disease (CJD, sporadic or familial), Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). Prion diseases can be differentiated into three etiological categories: spontaneous (sporadic CJD), inherited (familial CJD, FFI, and GSS) and acquired (variant CJD and iatrogenic CJD).

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

Background: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown.

Methods And Results: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study.

Creutzfeldt-Jakob disease and other prion diseases.

Prion diseases share common clinical and pathological characteristics such as spongiform neuronal degeneration and deposition of an abnormal form of a host-derived protein, termed prion protein. The characteristic features of prion diseases are long incubation times, short clinical courses, extreme resistance of the transmissible agent to degradation and lack of nucleic acid involvement. Sporadic and genetic forms of prion diseases occur worldwide, of which genetic forms are associated with mutations in PRNP.

KCNA2 IgG autoimmunity in neuropsychiatric diseases.

Background: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice.

Design / Methods: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses.

Nuclear face of Tau: an inside player in neurodegeneration.

Tau (Tubulin associated unit) protein is a major hallmark of Alzheimer's disease (AD) and tauopathies. Tau is predominantly an axonal protein with a crucial role in the stabilization and dynamics of the microtubules. Since the discovery of Tau protein in 1975, research efforts were concentrated on the pathophysiological role of Tau protein in the context of the microtubules.

Effect of SARS-CoV-2 Incidence and Immunisation Rates on Sporadic Creutzfeldt-Jakob Disease Incidence.

Background: Recent case studies and media outlets have hypothesised an effect of SARS-CoV-2 infection and immunisation on the development or progression of neurodegenerative diseases such as Alzheimer's disease or sporadic Creutzfeldt-Jakob disease (sCJD).

Objectives: This study aims to identify potential associations of SARS-CoV-2 infections and SARS-CoV-2 immunisation with sCJD incidence, disease duration, and age of onset.

Method: We used data from a prospective sCJD surveillance study in Germany (2016-2022) and publicly available datasets of SARS-CoV-2 cases and vaccination numbers in Germany for the years 2020-2022.

Differential interactome mapping of aggregation prone/prion-like proteins under stress: novel links to stress granule biology.

Background: Aberrant stress granules (SGs) are emerging as prime suspects in the nucleation of toxic protein aggregates. Understanding the molecular networks linked with aggregation-prone proteins (prion protein, synuclein, and tau) under stressful environments is crucial to understand pathophysiological cascades associated with these proteins.

Methods: We characterized and validated oxidative stress-induced molecular network changes of endogenous aggregation-prone proteins (prion protein, synuclein, and tau) by employing immunoprecipitation coupled with mass spectrometry analysis under basal and oxidative stress conditions.