Biology subjects

Gaurav, R.

Publications and source records attributed to Gaurav, R..

4 recordsLinked to original sources

bioRxiv2025

Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease

INTRODUCTIONThe locus coeruleus (LC) is among the first sites of tau pathology in Alzheimers disease (AD) and may seed neocortical tau. METHODSWe used longitudinal neuromelanin-sensitive MRI to assess LC integrity in vivo in a cohort of cognitively unimpaired older adults with familial risk of AD in relation to tau and amyloid PET and long-term cognitive trajectories. RESULTSWe showed that both LC integrity at baseline and its rate of degeneration over time independently predicted a neocortical pattern of tau deposition. In keeping with the known function of the LC, neuropsychological tests showed that LC integrity at baseline predicted changes in attention. Finally, we found that longitudinal LC degeneration correlated with memory decline in people with elevated neocortical amyloid burden. DISCUSSIONOur findings underscore the importance of LC in AD pathogenesis. Longitudinal measurement of LC degeneration may help distinguish trajectories of age-related cognitive decline and early AD.

neuroscience↗

bioRxiv2024

The role of dopaminergic, cholinergic and noradrenergic networks in hyposmia in Parkinson's disease

BackgroundOlfactory impairment is frequently observed in Parkinsons disease (PD) before motor symptom onset. Patients with isolated rapid eye movement sleep behaviour disorder (iRBD) are at risk to develop PD and present olfactory dysfunction. Subcortical neuromodulatory nuclei including the substantia nigra, the nucleus basalis of Meynert, and the locus coeruleus, may all contribute to olfactory dysfunction. ObjectiveThe objective of this study was to understand the network alterations underlying olfactory dysfunction in PD and in the early prodromal iRBD patients using multimodal MRI. MethodsPD (n = 107), iRBD patients (n = 35) and healthy controls (HC, n = 39) were recruited from the ICEBERG cohort for a cross-sectional study. We separated subjects in Healthy Controls, iRBD patients, and PD patients with or without RBD and with or without anosmia. Olfactory, motor, and cognitive scores were assessed and combined with multimodal imaging. ResultsWe found that olfaction positively correlated with (i) striatal DaT signal in PD patients; (ii) neuromelanin contrast in the locus coeruleus and (iii) Nucleus Basalis of Meynert grey matter (GM) volume in all patients. These signals were uncorrelated with motor and cognitive scores. Functional connectivity was reduced in regions of the cholinergic olfactory network in anosmic patients. Functional connectivity was also reduced in the noradrenergic network of patients with RBD. DiscussionOur results indicate the implication of the cholinergic network in PD patients with anosmia and a contribution of the noradrenergic network to olfactory dysfunction, only in patients with RBD.

neuroscience↗

bioRxiv2024

Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model

Studies in animal models of Parkinsons disease (PD) suggested that the accumulation of the neuromelanin (NM), a pigment contained in nigral dopaminergic neurons, could trigger neurodegeneration above a pathogenic threshold. Here we investigated this hypothesis using NM-sensitive MRI in rodents and in patients with isolated rapid eye movement sleep disorders (iRBD) subjects, a prodromal phase of parkinsonism, and early PD. We first combined NM-sensitive MRI and histology to study NM accumulation and neurodegeneration in a humanized rat model of PD. NM-MRI signal changes were biphasic with an initial increase due to the accumulation of NM in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with iRBD, NM-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early PD and converted iRBD patients, NM-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that NM-sensitive MRI is a marker of the intracellular NM accumulation up to a threshold then of neuronal degeneration beyond this threshold and agree with the hypothesis of a pathogenic threshold of NM triggering neurodegeneration.

neuroscience↗

bioRxiv2020

High-Throughput Analysis of Lung Immune Cells in a Murine Model of Rheumatoid Arthritis-Associated Lung Disease

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, autoreactive/suppressor), 5 macrophages (airspace, differentiating/recruited, recruited, resident/interstitial, and proliferative airspace), 2 T-cells (differentiating and effector), and a single cluster each of inflammatory monocytes, dendritic cells, B-cells and natural killer cells. Inflammatory monocytes, autoreactive/suppressor neutrophils, and recruited/differentiating macrophages were predominant with arthritis induction (CIA and CIA+ODE). By specific lung cell isolation, several interferon-related and autoimmune genes were disproportionately expressed among CIA and CIA+ODE (e.g. Oasl1, Oas2, Ifit3, Gbp2, Ifi44, and Zbp1), corresponding to RA and RA-associated lung disease. Monocytic myeloid-derived suppressor cells were reduced, while complement genes (e.g. C1s1 and Cfb) were uniquely increased in CIA+ODE mice across cell populations. Recruited and inflammatory macrophages/monocytes and neutrophils expressing interferon-, autoimmune-, and complement-related genes might contribute towards pro-fibrotic inflammatory lung responses following airborne biohazard exposures in setting of autoimmune arthritis and could be predictive and/or targeted to reduce disease burden.

immunology↗