Browsing by Author "Sasanka Chakrabarti"

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Acute Cardiac Events After ChAdOx1 nCoV-19 Corona Virus Vaccine: Report of Three Cases
(Lippincott Williams and Wilkins, 2022) Rohit Singh; Sankha Shubhra Chakrabarti; Indrajeet Singh Gambhir; Ashish Verma; Ishan Kumar; Soumik Ghosh; Ashutosh Tiwari; Gourav Chandan; Sasanka Chakrabarti; Upinder Kaur
[No abstract available]
Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells
(Taylor and Francis Ltd., 2024) Upasana Ganguly; Sukhpal Singh; Aritri Bir; Arindam Ghosh; Sankha Shubhra Chakrabarti; Reena V. Saini; Luciano Saso; Marco Bisaglia; Sasanka Chakrabarti
Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. Ferroptosis is activated by diverse triggers and inhibited by ferrostatin-1 and liproxstatin-1, apart from iron chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding the final executioner of cell death subsequent to the accumulation of ROS. This study uses a typical inducer of ferroptosis such as erastin on SH-SY5Y cells, and shows clearly that ferroptotic death of cells is accompanied by the loss of mitochondrial membrane potential and intracellular ATP content along with an accumulation of oxidative stress markers. All these are prevented by ferrostatin-1 and liproxstatin-1. Additionally, cyclosporine A prevents mitochondrial alterations and cell death induced by erastin implying the crucial role of mitochondrial permeability transition pore (mPTP) activation in ferroptotic death. Furthermore, an accumulation of α-synuclein occurs during erastin induced ferroptosis which can be inhibited by ferrostatin-1 and liproxstatin-1. When the knock-down of α-synuclein expression is performed by specific siRNA treatment of SH-SY5Y cells, the mitochondrial impairment and ferroptotic death of the cells induced by erastin are markedly prevented. Thus, α-synuclein through the involvement of mPTP appears to be the key executioner protein of ferroptosis induced by erastin, but it needs to be verified if it is a generalized mechanism of ferroptosis by using other inducers and cell lines. © 2024 Informa UK Limited, trading as Taylor & Francis Group.
Alpha-synuclein, proteotoxicity and parkinson's disease: Search for neuroprotective therapy
(Bentham Science Publishers B.V., 2018) Upasana Ganguly; Sankha Shubhra Chakrabarti; Upinder Kaur; Anwesha Mukherjee; Sasanka Chakrabarti
Background: There is a growing body of evidence in animal and cell based models of Parkinson's disease (PD) to suggest that overexpression and / or abnormal accumulation and aggregation of α-synuclein can trigger neuronal death. This important role of α-synuclein in PD pathogenesis is supported by the fact that duplication, triplication and mutations of α-synuclein gene cause familial forms of PD. Methods: A review of literature was performed by searching PubMed and Google Scholar for relevant articles highlighting the pathogenic role of α-synuclein and the potential therapeutic implications of targeting various pathways related to this protein. Results: The overexpression and accumulation of α-synuclein within neurons may involve both transcriptional and post-transcriptional mechanisms including a decreased degradation of the protein through proteasomal or autophagic processes. The mechanisms of monomeric α-synuclein aggregating to oligomers and fibrils have been investigated intensively, but it is still not certain which form of this natively unfolded protein is responsible for toxicity. Likewise the proteotoxic pathways induced by α-synuclein leading to neuronal death are not elucidated completely but mitochondrial dysfunction, endoplasmic reticulum (ER) stress and altered ER-golgi transport may play crucial roles in this process. At the molecular level, the ability of α-synuclein to form pores in biomembranes or to interact with specific proteins of the cell organelles and the cytosol could be determining factors in the toxicity of this protein. Conclusion: Despite many limitations in our present knowledge of physiological and pathological functions of α-synuclein, it appears that this protein may be a target for the development of neuroprotective drugs against PD. This review has discussed many such potential drugs which prevent the expression, accumulation and aggregation of α-synuclein or its interactions with mitochondria or ER and thereby effectively abolish α-synuclein mediated toxicity in different experimental models. © 2018 Bentham Science Publishers.
Ceramide and sphingosine-1-phosphate in cell death pathways: Relevance to the pathogenesis of Alzheimer’s disease
(Bentham Science Publishers B.V., 2016) Sankha Shubhra Chakrabarti; Aritri Bir; Jit Poddar; Maitrayee Sinha; Anirban Ganguly; Sasanka Chakrabarti
The metabolic turnover of sphingolipids produces several signaling molecules that profoundly affect the proliferation, differentiation and death of cells. In particular, an enormous body of information is available that defines the varied role of ceramide and sphingosine-1-phosphate in cell death and survival. This review specifically examines the role of ceramide and sphingosine-1- phosphate in triggering neuronal death in Alzheimer’s disease by analyzing the data from post-mortem studies and experimental research. There is compelling evidence that ceramide plays a key role in the neurodegeneration and amyloidogenesis occurring in the brain in Alzheimer’s disease. Further, it appears that ceramide and amyloid beta protein orchestrate an attack on mitochondria to set in the path-ways of cell death. However, the complexity of metabolic and signaling pathways of sphingolipid derivatives precludes an immediate identification of effective drug targets for the therapy of Alzheimer’s disease. © 2016 Bentham Science Publishers.
COVID-19 in India: Are biological and environmental factors helping to stem the incidence and severity?
(International Society on Aging and Disease, 2020) Sankha Shubhra Chakrabarti; Upinder Kaur; Anindita Banerjee; Upasana Ganguly; Tuhina Banerjee; Sarama Saha; Gaurav Parashar; Suvarna Prasad; Suddhachitta Chakrabarti; Amit Mittal; Bimal Kumar Agrawal; Ravindra Kumar Rawal; Robert Chunhua Zhao; Indrajeet Singh Gambhir; Rahul Khanna; Ashok K. Shetty; Kunlin Jin; Sasanka Chakrabarti
The ongoing Corona virus (COVID-19) pandemic has witnessed global political responses of unimaginable proportions. Many nations have implemented lockdowns that involve mandating citizens not to leave their residences for non-essential work. The Indian government has taken appropriate and commendable steps to curtail the community spread of COVID-19. While this may be extremely beneficial, this perspective discusses the other reasons why COVID-19 may have a lesser impact on India. We analyze the current pattern of SARS-CoV-2 transmission, testing, and mortality in India with an emphasis on the importance of mortality as a marker of the clinical relevance of COVID-19 disease. We also analyze the environmental and biological factors which may lessen the impact of COVID-19 in India. The importance of cross-immunity, innate immune responses, ACE polymorphism, and viral genetic mutations are discussed. © 2020 Chakrabarti S et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cross-immunity and trained immunity in explaining variable COVID-19 mortality—Guidance for future pandemics
(John Wiley and Sons Inc, 2021) Sasanka Chakrabarti; Sankha S. Chakrabarti; Upinder Kaur; Bimal K. Agrawal; Upasana Ganguly; Kunlin Jin
[No abstract available]
Did COVID-19 or COVID-19 Vaccines Influence the Patterns of Dengue in 2021? An Exploratory Analysis of Two Observational Studies from North India
(American Society of Tropical Medicine and Hygiene, 2023) Upinder Kaur; Parth Jethwani; Shraddha Mishra; Amol Dehade; Ashish Kumar Yadav; Sasanka Chakrabarti; Sankha Shubhra Chakrabarti
Dengue experienced a rise in disease burden in 2021 in specific regions of India. We aimed to explore the risk factors of dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era and performed an exploratory analysis involving participants from two prior observational studies conducted from February 2021 to April 2022 in a tertiary hospital in North India. Health care workers constituted the majority of the study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: COVID-No Vaccine, Vaccine-No COVID (VNC), COVID After Vaccine (CAV), Vaccine After COVID (VAC), and No Vaccine-No COVID (NVNC) groups. The occurrence of laboratory-confirmed dengue and severe forms of dengue were the main outcomes of interest. A total of 1,701 participants (1,520 vaccinated, 181 unvaccinated) were included. Of these, symptomatic dengue occurred in 133 (7.8%) and was “severe” in 42 (31.6%) cases. Individuals with a history of COVID-19 in 2020 had a 2-times-higher odds of developing symptomatic dengue (P 5 0.002). The VAC group had 3.6 (P 5 0.019)-, 2 (P 5 0.002)-, and 1.9 (P 5 0.01)-times-higher odds of developing symptomatic dengue than the NVNC, VNC, and CAV groups, respectively. The severity of dengue was not affected by COVID-19 vaccination but with marginal statistical significance, a 2-times-higher risk of severe dengue was observed with any COVID-19 of the past (P 5 0.08). We conclude that COVID-19 may enhance the risk of developing symptomatic dengue. Future research should explore the predisposition of COVID-19-recovered patients toward other viral illnesses. Individuals receiving COVID-19 vaccines after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-dependent enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals. Copyright © 2023 The author(s)
Dimethyl-2-oxoglutarate but not antioxidants prevents glucose hypometabolism induced neural cell death: implications in the pathogenesis and therapy of Alzheimer's disease
(Elsevier B.V., 2025) Aman Chauhan; Karanpreet Bhutani; Aritri Bir; Ajay Singh; Sankha Shubhra Chakrabarti; Adesh K. Saini; Sasanka Chakrabarti; Arindam Ghosh
Cerebral glucose hypometabolism is a cardinal molecular signature of Alzheimer's disease, and its role in the pathogenesis of this disorder is under intensive study in both animal and cell-based models. In the current study, we exposed SH-SY5Y cells (human neuroblastoma cell line) over a period of 48 h to DRB18, an inhibitor of multiple glucose transporters, in different concentrations to develop a state of glucose hypometabolism. Under this metabolic insult, in SH-SY5Y cells a profound dose-dependent neural cell death, an increased production of reactive oxygen radicals, mitochondrial membrane depolarization and a depletion of cellular ATP content were noted; these effects were not prevented by lipid-soluble novel antioxidants such as ferrostatin-1 and liproxstatin-1 or by a general water-soluble antioxidant like N-acetylcysteine. However, dimethyl-2-oxoglutarate, the cell-permeable analogue of 2-oxoglutarate (α-ketoglutarate) which can serve as an alternative fuel during glucose hypometabolism partially prevented both mitochondrial impairments and neural cell death. Thus, dimethyl-2-oxoglutarate may be explored further as a potential neuroprotective compound for Alzheimer's disease, and its effect on amyloid beta metabolism and homeostasis should be examined under glucose hypometabolic stress. © 2025 The Authors
Effectiveness of ChAdOx1 nCoV-19 vaccine during the delta (B.1.617.2) variant surge in India
(Elsevier Ltd, 2022) Sasanka Chakrabarti; Sankha Shubhra Chakrabarti; Gourav Chandan; Upinder Kaur; Bimal Kumar Agrawal
[No abstract available]
GLUT inhibitor WZB117 induces cytotoxicity with increased production of amyloid-beta peptide in SH-SY5Y cells preventable by beta-hydroxybutyrate: implications in Alzheimer’s disease
(Springer Science and Business Media Deutschland GmbH, 2023) Gourav Chandan; Upasana Ganguly; Soumya Pal; Sukhpal Singh; Reena V. Saini; Sankha Shubhra Chakrabarti; Adesh K. Saini; Sasanka Chakrabarti
Background: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer’s disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer’s disease. Methods: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of β-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. Results: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid β peptide (Aβ42). All the effects of WZB117 could be markedly prevented by co-treatment with β-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. Conclusion: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer’s disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models. © 2023, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.
Identifying the mechanisms of α-synuclein-mediated cytotoxicity in Parkinson's disease: New insights from a bioinformatics-based approach
(Future Medicine Ltd., 2020) Sankha S. Chakrabarti; Venkatadri S. Sunder; Upinder Kaur; Sapna Bala; Priyanka Sharma; Manjari Kiran; Ravindra K. Rawal; Sasanka Chakrabarti
Aim: A large body of evidence has implicated the cytotoxicity of α-synuclein in Parkinson's disease (PD). We planned to use a bioinformatics-based approach to gain further insight into this process. Materials & methods: Using STRING version 10, we identified interacting proteins of α-synuclein. Using α-synuclein and one of these interactors involved in apoptosis as query proteins, we identified other linked proteins. We further analyzed the interactions between some of these proteins by Protein-Protein Docking using ClusPro. Results: We identified BAX as an interacting protein of α-synuclein. Interactions of α-synuclein and BAX as well as BAX and BCL2L1 were determined. Conclusion: The interaction of α-synuclein and BAX could play a crucial role in the cell death process of PD where apoptosis and mitochondrial permeability transition-driven necrosis may coexist. © 2020 Sankha Shubhra Chakrabarti.
Interaction of α-synuclein and Parkin in iron toxicity on SH-SY5Y cells: Implications in the pathogenesis of Parkinson's disease
(Portland Press Ltd, 2020) Upasana Ganguly; Anindita Banerjee; Sankha Shubhra Chakrabarti; Upinder Kaur; Oishimaya Sen; Roberto Cappai; Sasanka Chakrabarti
The toxicity of accumulated α-synuclein plays a key role in the neurodegeneration of Parkinson's disease (PD). This study has demonstrated that iron in varying concentrations (up to 400 mM) causes an increase in α-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down α-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). These results indicate that iron cytotoxicity is mediated by α-synuclein acting on mitochondria. Likewise siRNA mediated knock-down of Parkin causes an accumulation of α-synuclein accompanied by mitochondrial dysfunction and cell death during 48 h incubation under basal conditions, but these changes are not further aggravated by co-incubation with iron (400 mM). We have also analyzed mitochondrial dysfunction and cell viability in SH-SY5Y cells under double knock-down (α-synuclein and Parkin concurrently) conditions during incubation for 48 h with or without iron. Our results tend to suggest that iron inactivates Parkin in SH-SY5Y cells and thereby inhibits the proteasomal degradation of α-synuclein, and the accumulated α-synuclein causes mitochondrial dysfunction and cell death. These results have implications in the pathogenesis of sporadic PD and also familial type with Parkin mutations. © 2020 The Author(s).
Lecanemab: More Questions Than Answers!
(Adis, 2024) Upinder Kaur; Jaideep Reddy; Ashutosh Tiwari; Sasanka Chakrabarti; Sankha Shubhra Chakrabarti
The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer’s disease. Lecanemab, an anti-amyloid beta monoclonal antibody, is the first Alzheimer’s disease drug targeting amyloid beta that has shown statistically significant cognitive benefits in phase III trials. However, there have been many questions raised over the clinical relevance of the otherwise minimal cognitive improvements. Furthermore, its rapid approval has been mired in controversy, in addition to the reports of adverse events such as amyloid-related imaging abnormalities and several deaths of participants in the lecanemab trials. Here, we analyze the evidence supporting lecanemab as an amyloid beta therapy and also discuss the concerns raised about its efficacy and safety. © 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Of cross-immunity, herd immunity and country-specific plans: Experiences from COVID-19 in India
(International Society on Aging and Disease, 2020) Sankha Shubhra Chakrabarti; Upinder Kaur; Anup Singh; Suddhachitta Chakrabarti; Manigreeva Krishnatreya; Bimal Kumar Agrawal; Amit Mittal; Amit Singh; Rahul Khanna; Indrajeet Singh Gambhir; Kunlin Jin; Sasanka Chakrabarti
India has witnessed a high number of COVID-19 cases, but mortality has been quite low, and most cases have been asymptomatic or mild. In early April, we had hypothesized a low COVID-19 mortality in India, based on the concept of cross-immunity. The presence of cross-immunity is presumed to lead to a milder course of disease and allow the time necessary for the development of adaptive immunity by the body to eliminate the virus. Evidence supporting our hypothesis has started showing up. Multiple studies have shown the generation of different T cell subsets and B cells responding to epitopes of viral proteins, especially of the spike protein, as a part of adaptive immunity against SARS-CoV-2. Cross-reactive T-cells have been demonstrated in patients who have been previously exposed to endemic coronaviruses. The interplay of cross-immunity and herd immunity is apparent in the COVID-19 scenario in India from the presence of a large number of asymptomatic or mild cases, a low infection-fatality ratio and a generally flat curve of percentage positivity of cases with respect to total testing, both in periods of strict lock-down and step-wise unlocking. It seems that cross-immunity resulted in faster generation of herd immunity. Although the initial restrictive measures such as lockdown prevented the rapid spread of the outbreak, further extension of such measures and overly expensive ones such as enhanced testing in India will result in a huge burden on the health economics as well as the society. Hence, we propose a restructuring of the health services and approach to COVID-19. The restructured health services should move away from indiscriminate testing, isolation and quarantine, and instead, the emphasis should be on improving facilities for testing and management of only critical COVID cases and the replacement of complete lockdowns by the selective isolation and quarantine of susceptible persons such as the aged and those with co-morbidities. In the process of describing India-specific plans, we emphasize why the development of country-specific plans for tackling epidemics is important, instead of adopting a “one policy fits all” approach. Copyright: © 2020 Chakrabarti SS. et al.
Oxidative Stress, Neuroinflammation, and NADPH Oxidase: Implications in the Pathogenesis and Treatment of Alzheimer's Disease
(Hindawi Limited, 2021) Upasana Ganguly; Upinder Kaur; Sankha Shubhra Chakrabarti; Priyanka Sharma; Bimal Kumar Agrawal; Luciano Saso; Sasanka Chakrabarti
NADPH oxidase as an important source of intracellular reactive oxygen species (ROS) has gained enormous importance over the years, and the detailed structures of all the isoenzymes of the NADPH oxidase family and their regulation have been well explored. The enzyme has been implicated in a variety of diseases including neurodegenerative diseases. The present brief review examines the body of evidence that links NADPH oxidase with the genesis and progression of Alzheimer's disease (AD). In short, evidence suggests that microglial activation and inflammatory response in the AD brain is associated with increased production of ROS by microglial NADPH oxidase. Along with other inflammatory mediators, ROS take part in neuronal degeneration and enhance the microglial activation process. The review also evaluates the current state of NADPH oxidase inhibitors as potential disease-modifying agents for AD. © 2021 Upasana Ganguly et al.
Protective effects of cyclosporine A on neurodegeneration and motor impairment in rotenone-induced experimental models of Parkinson's disease
(Elsevier B.V., 2022) Sukhpal Singh; Upasana Ganguly; Soumya Pal; Gourav Chandan; Rahul Thakur; Reena V. Saini; Sankha Shubhra Chakrabarti; Bimal K. Agrawal; Sasanka Chakrabarti
The development of neuroprotective drugs targeting mitochondria could be an important strategy in combating the progressive clinical course of Parkinson's disease. In the current study, we demonstrated that in SH-SY5Y cells (human dopaminergic neuroblastoma cell line), rotenone caused a dose-dependent (0.25–1 μM) and time-dependent (up to 48 h) loss of cell viability and a loss of cellular ATP content with mitochondrial membrane depolarization and an increased formation of reactive oxygen species; all these processes were markedly prevented by the mitochondrial permeability transition pore blocker cyclosporine A, which did not affect complex I inhibition by rotenone. The nuclear morphology of rotenone-treated cells for 48 h indicated the presence of both necrosis and apoptosis. We then examined the effects of cyclosporine A on the rotenone-induced model of Parkinson's disease in Wistar rats. Cyclosporine A significantly improved the motor deficits and prevented the loss of nigral dopaminergic neurons projecting into the striatum in rotenone-treated rats. Being a marketed immuno-suppressive drug, cyclosporine A should be further evaluated for its putative neuroprotective action in Parkinson's disease. © 2022 Elsevier B.V.
Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer’s disease: The NF-κB connection
(Bentham Science Publishers B.V., 2015) Upinder Kaur; Priyanjalee Banerjee; Aritri Bir; Maitrayee Sinha; Atanu Biswas; Sasanka Chakrabarti
Oxidative stress and inflammatory response are important elements of Alzheimer's disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-κBsignaling cascade has been discussed in the end. © 2015 Bentham Science Publishers.
Reserpine inhibition of lipid peroxidation and protein phosphorylation in rat brain
(1986) Sasanka Chakrabarti; Sajal Kumar; Raj Shankar
[No abstract available]
Role of oxidative stress in the pathogenesis of metabolic syndrome
(Elsevier, 2023) Sankha Shubhra Chakrabarti; Luciano Saso; Sapna Bala; Sarmistha Saha; Elisabetta Profumo; Brigitta Buttari; Sasanka Chakrabarti
Metabolic syndrome is a composite of the inter-related entities obesity, hypertension, insulin resistance, and dyslipidaemia which presents differently in different people. While risk factors of metabolic syndrome include over-nutrition and lack of physical activity, the interaction of these with genetic risk traits and individual phenotypic variations is responsible for the development of clinical manifestations. Mitochondrial dysfunction and oxidative stress have been reported widely to be a prominent part of the pathogenetic cascade of metabolic syndrome. In this chapter, we would discuss the entity of oxidative stress, the role it plays in the pathogenesis of metabolic syndrome, and also the relationship between oxidative stress and metabolic syndrome. Prominent tissue or organ-specific effects of oxidative stress with emphasis on the adipose tissue, skeletal muscle, liver, and the cardiovascular and endocrine systems would be described. We would also discuss the interplay between oxidative stress, inflammation, and insulin resistance and briefly about circulating oxidative stress markers and probable therapeutic strategies directed against oxidative stress which may be of benefit in metabolic syndrome. © 2024 Elsevier Inc. All rights reserved.
Serum 24-hydroxycholesterol in probable Alzheimer's dementia: Reexploring the significance of a tentative Alzheimer's disease biomarker
(Blackwell Publishing Ltd, 2019) Debashree Roy; Sankha Shubhra Chakrabarti; Anindita Banerjee; Pallav Sharma; Atanu Biswas; Sasanka Chakrabarti
Objective: This study measured and analyzed the serum levels of 24-hydroxycholesterol in patients with probable Alzheimer's disease (AD) and age-/sex-matched controls. Methods: A case-control study involving 40 AD patients and 40 controls was performed at a tertiary neurological teaching hospital in eastern India. Blood and serum samples were collected for APOE genotyping and 24-hydroxycholesterol levels, respectively. Results: Serum 24-hydroxycholesterol was significantly lower in AD patients compared to controls (median concentration: controls, 47.14 ng/mL (interquartile range, 16.34); AD patients, 32.93 ng/mL (interquartile range, 9.45); P < 0.001) but showed no significant correlation with Mini Mental State Examination (MMSE) score in AD cases (r = −0.169, P = 0.298) or in controls (r = 0.18, P = 0.26). No statistically significant difference was observed between serum 24-hydroxycholesterol levels of the APOE4-positive and -negative subgroups in AD patients (P = 0.79). Findings were consistent and unchanged even when the ratio of serum 24-hydroxycholesterol to serum total cholesterol was considered. Conclusion: The decreased 24-hydroxycholesterol level in peripheral circulation in AD cases observed in the present study may suggest its role in AD pathogenesis. The lack of a clear correlation between serum levels of 24-hydroxycholesterol and MMSE score—a surrogate marker of AD severity—raises the question as to whether 24-hydroxycholesterol level declines with decreasing neuronal mass or whether the steroid continues to play a protective role. © 2019 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.