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Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists with Alzheimer's disease (AD). Due to the reversible nature of iNPH when promptly treated, a lot of studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim of the present study was to determine the rate of beta-amyloid pathology and AD co-pathology by measuring AD CSF biomarkers, namely, amyloid beta with 42 and 40 amino acids (Aβ42), the Aβ42/Aβ40 ratio, total Tau protein (t-Tau) and phosphorylated Tau protein at threonine 181 (p-Tau), in a cohort of iNPH patients, as well as to investigate the possible associations among CSF biomarkers and iNPH neuropsychological profiles. Fifty-three patients with iNPH were included in the present study. CSF Aβ42, Aβ40, t-Tau and p-Tau were measured in duplicate with double-sandwich ELISA assays. The neuropsychological evaluation consisted of the Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test and CLOX drawing tests 1 and 2. After statistical analysis, we found that amyloid pathology and AD co-pathology are rather common in iNPH patients and that higher values of t-Tau and p-Tau CSF levels, as well as the existence of the AD CSF profile, are associated with more severe memory impairment in the study patients. In conclusion, our study has confirmed that amyloid pathology and AD-co-pathology are rather common in iNPH patients and that CSF markers of AD pathology and t-Tau are associated with a worse memory decline in these patients.
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http://dx.doi.org/10.3390/biomedicines12081898 | DOI Listing |
Mol Ther Methods Clin Dev
December 2024
Preclinical Safety (PCS), Novartis Biomedical Research, Cambridge, MA, USA.
Administration of AAV-based gene therapies into the intra-cerebrospinal fluid (CSF) compartments via routes such as lumbar puncture (LP) has been implemented as an alternative to intravenous dosing to target the CNS regions. This route enables lower doses, decreases systemic toxicity, and circumvents intravascular pre-existing anti-AAV antibodies. In this study, AAV9-GFP vectors were administered via LP to juvenile cynomolgus macaques with and without pre-existing serum anti-AAV9 antibodies at a 5.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
University of Pompeu Fabra (UPF), Barcelona, Spain.
Background: Cerebrospinal fluid (CSF) biomarkers of synaptic dysfunction, neuroinflammation, and glial response, complementing Alzheimer's disease (AD) core biomarkers, have improved the pathophysiological characterization of the disease. Here, we tested the hypothesis that the co-expression of multiple CSF biomarkers will help the identification of AD-like phenotypes when biomarker positivity thresholds are not met yet.
Methods: Two hundred and seventy cognitively unimpaired adults with family history (FH) of sporadic AD (mean age = 60.
Methods Mol Biol
December 2024
Proteomics, Bioanalytics Department, Nestlé Institute of Food Safety & Analytical Sciences, Nestlé Research, Lausanne, Switzerland.
Protein biomarker discovery in human biological fluids has greatly developed over the past two decades thanks to technological advances allowing deeper proteome coverage and higher sample throughput, among others. While blood samples are most commonly investigated due to their moderate ease of collection and high information content, other biological fluids such as cerebrospinal fluid (CSF) and urine are highly relevant for specific pathologies, such as brain and urologic diseases, respectively. Independently of the biofluid of interest, platforms that can robustly handle a large number of samples are essential in the discovery phase of a clinical study.
View Article and Find Full Text PDFJ Vet Intern Med
December 2024
Division of Clinical Neurology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Background: In dogs with idiopathic epilepsy (IE), 33% develop resistance to conventional anti-seizure medication (ASM) despite adequate treatment. In human medicine, an immune-mediated etiology is suspected in a subset of ASM-resistant patients with epilepsy and cerebrospinal fluid (CSF)-specific immunoglobulin G (IgG)-type oligoclonal bands (OCBs) have been detected. In dogs, cases of autoimmune encephalitis recently were reported.
View Article and Find Full Text PDFNeurology
January 2025
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Background And Objectives: To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments.
Methods: We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications.
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