👤 Mohit Parekh

Alzheimer's disease (AD) is moving toward earlier, biology-driven diagnosis, which increases the need for blood-based markers that are reliable, scalable, and interpretable across populations. This review integrates the AT(N) framework with a maturity model for circulating biomarkers. We first describe core and largely validated plasma measures, including LC-MS or automated immunoassay Aβ42/Aβ40 ratios, p tau217 and p tau231, glial fibrillary acidic protein (GFAP), and neurofilament light, and we relate them to recent multi-stakeholder recommendations on analytical performance and regulatory status. We then summarize replicated but context-dependent markers, such as soluble TREM receptors, CHI3L1, and MCP 1, which improve risk stratification when interpreted together with amyloid and tau. A separate section examines emerging readouts that capture central nervous system (CNS) processes indirectly, focusing on neuron-enriched extracellular vesicles (EVs) and EV-carried microRNA panels. These signatures are biologically plausible and often precede symptoms, although current datasets are small, Alzheimer's disease neuroimaging initiative (ADNI)-based, and require standardized pre-analytical handling and external validation before clinical triage can be recommended. We also discuss platform selection, comparing automated electrochemiluminescence (ECL) and single-molecule assays with LC-MS, and outline how composite plasma panels that include APOE genotype can support screen-confirm-monitor workflows in memory clinics. Finally, we propose a tiered implementation path in which genomic risk profiling and blood tests identify candidates for cerebrospinal fluid (CSF) or positron emission tomography (PET) studies. This shows how circulating and multi-omics biomarkers can be layered onto established plasma Amyloid beta (Aβ) and p tau assays to widen the measurable blood space in Alzheimer's disease. Show less

The objective of this study was to evaluate the efficacy of scraping without endothelial keratoplasty technique using a novel cell scraper for treating corneal endothelial dysfunction and explore the adjuvant effects of a ROCK inhibitor (ROCKi). Human donor tissues (n = 3) were mounted on an artificial anterior chamber, and one-half of the corneal endothelium was scraped with a novel cell scraper. The tissues were then stained with hematoxylin and eosin (H&E) to assess cell removal. In parallel, central peeling (descemetorhexis) using sharp acute forceps (n = 8) and cell scraping using a novel cell scraper (n = 8) was compared with and without ROCKi to investigate the wound healing response. RT-PCR analysis to assess the endothelial-to-mesenchymal transition using ZEB1 , SNAI1/2 , VIM , and CDH1/2 genes was performed after storage. An ex vivo surgical setup using an artificial anterior chamber demonstrated the feasibility and efficacy of using the cell scraper. Superior wound healing (88%) was observed in the endothelial cell-scraping group compared with Descemet membrane peeling (22%) at day 16. Application of ROCKi expedited wound healing after endothelial scraping (97%) and peeling (40%) compared with their respective controls at day 16. ROCKi treatment promoted endothelial-to-mesenchymal transition; however, with enhanced wound healing after cell scraping, endothelial cells formed a monolayer on native Descemet membrane compared with the peeling method. Scraping without endothelial keratoplasty can be performed effectively using the cell scraper and offers a potential alternative to endothelial keratoplasty, which can be effective in treating bullous keratopathy with healthy peripheral endothelial cells. ROCKi enhances wound healing, supporting further clinical testing and potentially delaying corneal tissue implantation. Show less

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor ( Show less

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in the Goto-Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular proteins (Gja1 and Gja4), intracellular Ca(2+) transport (Atp2a1 and Ryr2), cell membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control-sucrose group compared with control rats and in the GK-sucrose group compared with GK rats. The amplitude of the Ca(2+) transient was increased in myocytes from control-sucrose compared with control rats and decreased in GK-sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intracellular Ca(2+) transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet. Show less

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca(2+) transient were unaltered; however, the time-to-peak shortening was prolonged and time-to-half decay of the Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation-contraction coupling proteins that are associated with disturbances in myocyte shortening and intracellular Ca(2+) transport. Show less

Potential mechanisms accounting for the high cardiovascular death rates observed in Asian-Indians are dyslipidemia and insulin resistance. Polymorphisms in the APOC3 promoter (-455 T/C and -482 C/T) were frequently encountered in young Asian-Indians and they correlated with reduced concentrations of apolipoprotein A-I. Show less