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Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.
PLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
View Article and Find Full Text PDFA Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.
Neuro Oncol
December 2024
Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA.
Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Turner Institute for Brain and Mental Health & School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
Background: Plasma and cerebrospinal (CSF) biomarkers are promising candidates for detecting neuropathology. While CSF biomarkers directly reflect pathophysiological processes within the central nervous system, their requirement for a lumbar puncture is a barrier to their widespread scalability in practice. Therefore, we examined cross-sectional associations of plasma biomarkers of amyloid (Aβ42/Aβ40 and pTau-181), neurodegeneration (Neurofilament Light, NfL), and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP) with brain volume, cognition, and their corresponding CSF levels.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Existing biomarkers including cerebrospinal fluid and positron emission tomography for Alzheimer's disease (AD) diagnosis are relatively invasive and expensive. Application of exhaled breath collection and volatile organic compound (VOC) detection for AD diagnosis remains unclear.
Method: In this cross-sectional study, high-pressure photon ionization time-of-flight mass spectrometry (HPPI-ToF-MS) was used to detect VOCs from breath in three datasets and patients diagnosed as Parkinson's disease (PD).
Background: Neurofilament light chain (NfL) is a fluid biomarker of axonal damage reported to be elevated in cases with dementia, and particularly in FTD. In this study we evaluate the performance of a recently developed NfL assay to be analyzed through the Lumipulse chemiluminescent platform, which is frequently available in clinical settings for the study of AD core biomarkers.
Method: We evaluated CSF NfL levels using the Lumipulse G600II platform (Fujirebio, Iberia) in 70 cases, including 33 patients with AD (supported by CSF biomarkers consistent with an A+T+(N)+ classification scheme), 26 with confirmed FTD (typical phenotype and CSF with a A-T- profile), and 11 controls.
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