Biology subjects

Bhavane, R.

Publications and source records attributed to Bhavane, R..

3 recordsLinked to original sources

bioRxiv2026

Molecular MRI of Neuroinflammation in Alzheimer's Disease using a Folate-targeted Nanoprobe

Background: Neuroinflammation, driven by activated microglia, plays a central role in the pathogenesis of Alzheimer's disease (AD). Non-invasive imaging of neuroinflammation holds promise for advancing our understanding of disease mechanisms and evaluating anti-inflammatory therapeutic strategies. The folate receptor (FR), specifically its {beta} isoform, has been identified as a marker of pro-inflammatory myeloid cells in peripheral inflammatory diseases; however, its association with AD neuroinflammation remains unknown. In this work, we first determined FR expression in microglia in mouse models of AD and subsequently evaluated molecular MRI (mMRI) using a folate-targeted nanoprobe for in vivo imaging of the folate receptor expression. Methods and results: Microglial activation and FR expression in APP/PS1 and P301S transgenic mouse models of AD was measured using flow cytometry. A FR-targeted nanoprobe for mMRI was prepared by functionalizing high T1-relaxivity liposomal gadolinium nanoparticle with folic acid. Following intravenous injection, localization of the nanoprobe in the brains of aged transgenic and wild-type mice was measured using T1-weighted MRI. Post-mortem microscopy measured nanoprobe localization relative to microglia and amyloid pathology. In both mouse models, FR{beta} was significantly (p < 0.05) upregulated in pro-inflammatory microglia expressing TNF and IL-1{beta}. The folate-targeted nanoprobe demonstrated MR signal enhancement in the cortical and hippocampal regions of transgenic mice but not in wild type mice; non-targeted nanoprobe control did not demonstrate signal enhancement in brain of transgenic mice. Microscopy confirmed colocalization of FR-targeted nanoprobe with IBA1-positive microglia/macrophages and amyloid plaques. Conclusions: Pro-inflammatory microglia exhibit elevated levels of FR, and its measurement by non-invasive mMRI is a promising marker of neuroinflammation in AD.

neuroscience↗

bioRxiv2024

Accelerated amyloid deposition in SARS-CoV-2 infected mouse models of Alzheimer's disease

Familial Alzheimers disease (AD) involving known AD causing genes accounts for a small fraction of cases, the vast majority are sporadic. Neuroinflammation, secondary to viral infection, has been suggested as an initiating or accelerating factor. In this work we tested the hypothesis that SARS-CoV-2 (SCV2) viral infection accelerates the development of AD pathology in mouse models of AD. We profiled transcriptomic changes using transgenic APP/PSEN1 and P301S mouse models that develop AD pathology and k18hACE2 mice that express the humanized ACE2 receptor used by SCV2 to enter cells. This study identified the interferon and chemokine responses constituting key shared pathways between SCV2 infection and the development of AD pathology. Two transgenic mouse models of AD: APP/PSEN1 (develops amyloid pathology) and 3xTg AD (develops both amyloid and tau pathology) were crossed with k18-hACE2 mice to generate hybrid hACE2-3xTg and hACE2-APP/PSEN1 mice. Neuroinflammation and amyloid deposition in the brain of infected mice were imaged in vivo using molecular MRI (mMRI) probes and confirmed postmortem by histopathology. Results show that 11-14-month-old SCV2 infected hACE2-3xTg mice exhibit neuroinflammation 10 days post infection and 4-5-month-old hACE2-APP/PS1 hybrid mice develop amyloid deposits, while age-matched uninfected mice exhibit neither phenotype. This suggests that SCV2 infection could induce or accelerate AD when risk factors are present.

neuroscience↗

bioRxiv2021

Early Detection of Tau Pathology

While a definitive Alzheimers disease (AD) diagnosis remains a post-mortem exercise, the ATN Research Framework proposed by the National Institute on Aging and the Alzheimers Association utilizes a score representing the presence of amyloid deposits (A), tau deposits (T) and neuronal degeneration markers (N), with A+T+ necessary for a positive diagnosis. Current detection of tau pathology lags amyloid detection by years and by the time both markers are detected the disease is fairly advanced. We describe the development of a new generation of molecular imaging probes for in vivo detection of cells undergoing abnormal phosphorylation representing the initial stages of pTau pathology, potentially enabling a very early stage diagnosis of AD. We describe a novel nanoparticle formulation that binds such abnormally phosphorylating cells in a mouse model of tau pathology, enabling in vivo visualization of the hyperphosphorylative state by magnetic resonance imaging. Our results demonstrate the potential of this novel platform to identify a correlative marker signifying the development of future tau pathology, and has implications for early-stage diagnosis of Alzheimers disease.

neuroscience↗