Identification of a pathogenic mutation in in patients with amyotrophic lateral sclerosis.

Background And Objective: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.

Methods: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data.

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.

Diagnostic performance of plasma pTau 217, pTau 181, Aβ 1-42 and Aβ 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

Background: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.

Methods: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aβ/Aβ ratio.

Effects of storage conditions on the stability of blood-based markers for the diagnosis of Alzheimer's disease.

Objectives: Alzheimer's disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aβ1-42, Aβ1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples.

Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis.

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers.

Hypoechogenicity of the raphe nuclei as a biomarker of migraine: A case-control study, review, and meta-analysis.

Background And Purpose: Hypoechogenicity of the raphe nuclei (hR) has been related to major depression. Comorbidity between migraine and depression is bidirectional postulating a common mechanism of serotonergic dysfunction. We aimed to investigate the association between migraine and hR and its role as biomarker of migraine-associated depression and disease severity.

Isoform-selective decrease of glycogen synthase kinase-3-beta (GSK-3β) reduces synaptic tau phosphorylation, transcellular spreading, and aggregation.

It has been suggested that aberrant activation of glycogen synthase kinase-3-beta (GSK-3β) can trigger abnormal tau hyperphosphorylation and aggregation, which ultimately leads to neuronal/synaptic damage and impaired cognition in Alzheimer disease (AD). We examined if isoform-selective partial reduction of GSK-3β can decrease pathological tau changes, including hyperphosphorylation, aggregation, and spreading, in mice with localized human wild-type tau (hTau) expression in the brain. We used adeno-associated viruses (AAVs) to express hTau locally in the entorhinal cortex of wild-type and GSK-3β hemi-knockout (GSK-3β-HK) mice.