We measured serum and CSF beta 2-microglobulin (beta 2M) levels in HIV-1 seropositive individuals with and without dementia to determine the frequency and diagnostic utility of elevation of CSF beta 2M. We compared 34 samples from 27 patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive participants in the Multicenter AIDS Cohort Study, none of whom had progressive dementia. Neurosyphilis and CNS opportunistic processes were excluded in all subjects. We stratified the nondemented subjects by duration of HIV seropositivity and peripheral blood CD4 count. Compared with the nondemented group, demented subjects had significantly higher CSF total protein, IgG%, and CSF albumin/serum albumin ratios. A highly significant association was found between elevated CSF beta 2M and reduced CD4 count (p less than 0.0001). No significant differences were noted between the demented and nondemented groups in CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF beta 2M was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with dementia (p less than 0.0001). We derived a cutoff of 3.8 mg/l from the distribution of CSF beta 2M in the nondemented group. The determination of CSF beta 2M had a sensitivity of 44%, specificity of 90%, and a positive predictive value of 88% for diagnosis of HIV dementia when compared with nondemented subjects with CD4 counts less than 200. In those without dementia, there was a strong correlation between serum and CSF beta 2M (r = 0.50, p less than 0.0001), but in demented subjects CSF beta 2M was elevated independently of serum levels, suggesting that CSF beta 2M is produced within the brain in HIV dementia. In the absence of CNS opportunistic processes, elevated CSF beta 2M greater than 3.8 mg/l is a clinically useful marker for HIV dementia.
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http://dx.doi.org/10.1212/wnl.42.9.1707 | DOI Listing |
Pediatr Res
January 2025
Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI, USA.
Background: The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE).
Methods: Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network.
Brain
January 2025
Translational Neuroimaging Laboratory, Montreal Neurological Institute, H3A 2B4, Montreal, Canada.
Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.
View Article and Find Full Text PDFBackground: Although Amyloid-beta and Tau are the hallmarks of Alzheimer's Disease (AD), other protein pathways such as endothelial dysfunction may be involved and may precede cognitive symptoms. Our objective was to characterize the cerebrospinal fluid (CSF) proteomic profiles focusing on cardiometabolic-related protein pathways in individuals on the AD spectrum.
Methods: We performed CSF and plasma-targeted proteomics (276 proteins) from 354 participants of the Brain Stress Hypertension and Aging Program (BSHARP), of which 8% had preclinical AD, and 24% had MCI due to AD.
Mol Immunol
January 2025
Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Master Program of Pharmaceutical Manufacture, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address:
The immunoglobulin E (IgE) receptor FcεRI (Fc epsilon RI) plays a crucial role in allergic reactions. Recent studies have indicated that the interaction between FcεRIβ and the downstream protein phospholipase C beta 3 (PLCβ3) leads to the production of inflammatory cytokines. The aim of this study was to develop small molecules that inhibit the protein-protein interactions between FcεRIβ and PLCβ3 to treat allergic inflammation.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Psychiatry and Neuroscience, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.
Methods: Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical Alzheimer's Cognitive Composite (PACC), Clinical Dementia Rating (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
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