Your search for: 'author:("Joshi, Yash B.")' has returned 4 results. (0.05s) Save search

Authors: Joshi, Yash B. | Chu, Jin | Praticò, Domenico

Article Type: Research Article

Abstract: Several studies have linked stress with Alzheimer's disease (AD) vulnerability; however, the mechanism remains to be fully elucidated. In the current paper, we investigated the role of glucocortitcoids on the AD-like phenotype. We administered the glucocorticoid dexamethasone to Tg2576 mice for 4 weeks and then investigated its effect on memory, amyloid-β and tau levels, and metabolism. At the end of the treatment period, we observed that mice receiving dexamethasone had a significant impairment in the fear conditioning paradigm compared with controls. Dexamethasone-treated animals showed a significant increase in the amount of brain soluble Aβ40 levels, but no alteration in the …steady state levels of its precursor protein, AβPP, or in the major protease enzymes involved in its metabolism (i.e., ADAM-10, BACE-1, or γ-secretase complex). While total tau protein levels were unaltered between the two groups, we found that dexamethasone significantly reduced tau phosphorylation at specific sites that were mediated by decreases in glycogen synthase kinase-3β protein level activity. Finally, we observed a direct correlation between memory impairments and tau phosphorylation levels. Our study highlights the significant role that glucocorticoids play in exacerbating AD-like cognitive impairments via alteration of tau protein phosphorylation state. Show more

Keywords: Alzheimer's disease, transgenic animal model, stress, glucocorticoid

DOI: 10.3233/JAD-2012-120328

Citation: Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 167-176, 2012

Authors: Joshi, Yash B. | Di Meco, Antonio | Praticó, Domenico

Article Type: Short Communication

Abstract: Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) pathogenesis, and among them, the pro-inflammatory 5-lipoxygenase (5LO) enzyme. While previous work has shown that 5LO modulates the amyloidotic phenotype of AD, the exact metabolic product responsible for this biological action remains unknown. In this study, we challenged neuronal cells with leukotriene B4 (LTB4 ), a major 5LO product, and found that it increased amyloid-β formation whereby elevating the steady-state levels of the γ-secretase proteins, suggesting that LTB4 is the mediator of the 5LO effect. Therapies that by blocking 5LO activation suppress the formation of LTB4 or its action represent novel …AD therapeutic opportunities. Show more

Keywords: Alzheimer's disease, amyloid-β, γ-secretase, leukotriene B4, 5-lipoxygenase

DOI: 10.3233/JAD-131223

Citation: Journal of Alzheimer's Disease, vol. 38, no. 3, pp. 503-506, 2014

Authors: Swerdlow, Neal R. | Kotz, Juliana E. | Joshi, Yash B. | Talledo, Jo | Sprock, Joyce | Molina, Juan L. | Huisa, Branko | Huege, Steven F. | Romero, Jairo Alberto | Walsh, Michael J. | Delano-Wood, Lisa | Light, Gregory A.

Article Type: Short Communication

Abstract: Memantine’s benefits in Alzheimer’s disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual’s clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.

Keywords: Alzheimer’s disease, event-related potentials, memantine, neurocognition, prepulse inhibition

DOI: 10.3233/JAD-215029

Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1431-1438, 2021

Authors: Swerdlow, Neal R. | Joshi, Yash B. | Sprock, Joyce | Talledo, Jo | Molina, Juan L. | Delano-Wood, Lisa | Iwanaga, Dylan | Kotz, Juliana E. | Huege, Steven | Léger, Gabriel C. | Light, Gregory A.

Article Type: Research Article

Abstract: Background: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer’s disease (AD); conceivably, its acute impact on PPI might be used to predict a patient’s sensitivity to MEM’s therapeutic effects. Objective: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. Methods: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. Results: Fifteen out of 18 participants exhibited reliable startle responses. MEM did …not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p  < 0.04; d  = 0.40); this comparison reached a large effect size for the 60 ms interval (d  = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency (“latency facilitation”) and this effect was amplified after MEM (p  = 0.03; d  = 0.41; for 60 ms intervals, d  = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures. Conclusion: MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient’s neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a “biomarker” measured at the outset on treatment can predict sensitivity to MEM’s therapeutic effects. Show more

Keywords: Alzheimer’s disease, memantine, neurocognition, prepulse inhibition

DOI: 10.3233/JAD-220769

Citation: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 355-362, 2023