Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aß42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.

Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk.

OBJECTIVE: Few studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration. METHODS: In 706 cognitively normal adults, we examined whether 14 protein-based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma-based biomarkers of AD pathology (amyloid-ß [Aß]42/40 , tau phosphorylated at threonine-181 [pTau-181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aß and tau. In a separate cohort (n = 11,285), we examined whether protein-based health indicators associated with neurodegeneration also predict 25-year dementia risk. RESULTS: Greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with lower Aß42/40 and higher pTau-181, NfL, and GFAP levels, even in individuals without cardiovascular or kidney disease. Proteomic indicators of body fat percentage, lean body mass, and visceral fat were associated with pTau-181, NfL, and GFAP, whereas resting energy rate was negatively associated with NfL and GFAP. Together, these health indicators predicted 12, 31, 50, and 33% of plasma Aß42/40 , pTau-181, NfL, and GFAP levels, respectively. Only protein-based measures of cardiovascular risk were associated with reduced regional brain volumes; these measures predicted 25-year dementia risk, even among those without clinically defined cardiovascular disease. INTERPRETATION: Subclinical peripheral health may influence AD and neurodegenerative disease processes and relevant biomarker levels, particularly NfL. Cardiovascular health, even in the absence of clinically defined disease, plays a central role in brain aging and dementia. ANN NEUROL 2024;95:260-273.

Plasma proteins related to inflammatory diet predict future cognitive impairment.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aß42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

Addition of transglutaminase enzyme in camel milk yoghurt to increase its sensorial aspects.

Camel milk was obtained from A-block UVAS Ravi Campus Pattoki. After pasteurization at 72 °C (15 sec) it was cooled to 42 °C, then glutathione treated transglutaminase enzyme was added with the concentration of 0.5 g/300 mL, 1 g/300 mL, 1.5 g/300 mL, 2 g/300 mL while control sample with the addition of 1.5 g/300 mL gelatin. Then inoculation of milk was done with standard cultures of Yoghurt Lactobacillus delbrueckii subsp bulgaricus and Streptococcus thermophilus at the rate of 2% for 3-4 hours at 42 °C. Samples were stored at 4 °C and were analyzed on 1st day and 28th day of storage. In our findings, there was slight increase in sensorial properties of all the samples. It was also observed that syneresis was reduced with the increase of enzyme quantity.

Assessment of variability in the plasma 7k SomaScan proteomics assay.

SomaScan is a high-throughput, aptamer-based proteomics assay designed for the simultaneous measurement of thousands of proteins with a broad range of endogenous concentrations. In its most current version, the 7k SomaScan assay v4.1 is capable of measuring 7288 human proteins. In this work, we present an extensive technical assessment of this platform based on a study of 2050 samples across 22 plates. Included in the study design were inter-plate technical duplicates from 102 human subjects, which allowed us to characterize different normalization procedures, evaluate assay variability by multiple analytical approaches, present signal-over-background metrics, and discuss potential specificity issues. By providing detailed performance assessments on this wide range of technical aspects, we aim for this work to serve as a valuable resource for the growing community of SomaScan users.

Association of liver disease with brain volume loss, cognitive decline, and plasma neurodegenerative disease biomarkers.

Although liver dysfunction has been implicated in Alzheimer's disease (AD), it remains unknown how liver disease may influence the trajectory of brain and cognitive changes in older adults. We related self-reported liver disease to longitudinal measures of brain structure and cognition, as well as baseline measures of plasma AD/neurodegeneration biomarkers in the Baltimore Longitudinal Study of Aging. Liver disease was identified using ICD-9 classification codes. Brain volume and cognition were assessed serially using 3T-MRI and a cognitive battery. 1008, 2157, and 780 participants were included in the MRI, cognitive, and plasma biomarker analysis, respectively. After adjustment for confounders, liver disease was associated with accelerated decline in total brain and white matter volume, but not total gray matter or AD signature region volume. Although liver disease showed no relationship with domain-specific cognitive decline or plasma biomarkers, participants with a history of hepatitis demonstrated accelerated decline in verbal fluency and elevated neurofilament light. Results suggest all-cause liver disease may accelerate brain volume loss but does not appear to promote AD-specific neurocognitive changes.

Phytochemical screening, antimicrobial activity, in vitro and in vivo antioxidant activity of Berberis lycium Royle root bark extract.

Antioxidants are materials that scavenge or remove free radicals from living systems. The oxidation process ends in the production of free radicals. These free radicals are the chief birthplace of cancerous cells. Antioxidizing agents remove free radical intermediates by terminating oxidation processes by being oxidized themselves. On the other hand, infectious diseases affect the world on a large scale. To fight these diseases several synthetic compounds have been used. Plant based medications play important role in this regard. So, the current research aimed to investigate the antibacterial and antioxidant effect of Berberis lycium Royle root bark (BLR) extract. Berberis lycium Royle was used for phytochemical analysis and also as antimicrobial and antioxidant agents. The antimicrobial activity was evaluated by the agar well diffusion method. Current study revealed that BLR was rich in phytochemicals and toxic against tested pathogenic bacteria. BLR showed the highest activity against S. pyogenes (13.3±0.8 mm). The lowest antibacterial activity was reported against E. coli (0±0 mm). In case of minimum inhibitory concentration, it was observed that BLR with 10 µg/mL concentration showed the highest activity while 2.5 µg/mL of BLR showed the least inhibitory activity. The highest In vitro antioxidant activity was recorded as 65% at 100 µg/mL. In case of in vivo antioxidant activity level of CAT, GSH and SOD were decreased while that of MDA was enhanced in groups treated with CCl4 as compared to the control group. BLR extract treatment reversed all these changes significantly. Current results indicate that BLR is effective against bacterial pathogens and also has antioxidant potential.

Persistent Psychosis due to Single Dose of Ecstasy.

Ecstasy, a popular drug among the younger generation, the primary psychoactive component of which is 3,4-Methylenedioxymethamphetamine (MDMA), is rarely known to have acute psychiatric effects and when it does, it is usually short term. We describe a patient who presented to the emergency room in a psychotic state after using ecstasy recreationally. Given his aggressive behavior in the community and risk for self-harm, he was emergently hospitalized to ensure safety. He developed persistent psychotic symptoms (delusions) after one dose of recreational MDMA and the team had the opportunity to observe, monitor, and treat his psychosis. This case along with few other documented cases highlights the gaps in research about the chronic, persistent effects and long-term consequences of MDMA. It also suggests that neuropsychiatric symptoms may not be readily reversible after cessation of use. There is an emphasis on the need for physicians to inquire about MDMA use and include it in toxicology screenings and as a potential differential diagnosis.

Properties of HTLV-I transformed CD8+ T-cells in response to HIV-1 infection.

HIV-1 infection studies of primary CD8(+) T-cells are hampered by difficulty in obtaining a significant number of targets for infection and low levels of productive infection. Further, there exists a paucity of CD8-expressing T-cell lines to address questions pertaining to the study of CD8(+) T-cells in the context of HIV-1 infection. In this study, a set of CD8(+) T-cell clones were originated through HTLV-I transformation in vitro, and the properties of these cells were examined. The clones were susceptible to T-cell tropic strains of the virus and exhibited HIV-1 production 20-fold greater than primary CD4(+) T-cells. Productive infection resulted in a decrease in expression of CD8 and CXCR4 molecules on the surface of the CD8(+) T-cell clones and antibodies to these molecules abrogated viral binding and replication. These transformed cells provide an important tool in the study of CD8(+) T-cells and may provide important insights into the mechanism(s) behind HIV-1 induced CD8(+) T-cell dysfunction.