Evaluation of Apolipoprotein e4 allele as susceptible factor for neurodegenerative diseases among Eastern Indians

Introduction Apolipoprotein E (ApoE) and age have been identified as the major risk factors for several neurodegenerative disorders. Among the three major isoforms ( ApoE2, ApoE3 & ApoE4 ) of APOE, ApoE4 often shows ethnicity dependent association with neurodegenerative diseases. In the present study, we aim to determine the e4 allele/genotype frequency among the different neurodegenerative disorders and their correlation with several demographic and clinical parameters from eastern India. Material & Methods A total of 826 individuals were recruited for this study which includes 128 PD-MCI, 144 PDD, 90 DLB, 114 FTD, 94 AD and 256 unrelated neurologically controls from eastern India. Subjects were analysed for APOE genotype ( E2, E3 and E4 ) by PCR-RFLP techniques and Sanger sequencing. Results The APOE4 allele was significantly associated with each of the disease subtypes, selected for the study (P = 0.016 to 0.000), while e3 allele was predominant among controls. Further stratification of subjects identified significant overrepresentation of (a) positive family history for FTD (P = 0.0414) & AD (P = 0.029) and (b) early age at onset of for PDD (P = 0.0316) and FTD (P = 0.0034) among the e4 allele carriers. Furthermore, lowering of BMSE score was also observed among the e4 allele carriers of AD subjects (P = 0.0324). Conclusion There is a significant association of APOE4 allele with different neurodegenerative diseases influencing lowering of age at onset, BMSE score and positive family history among ethnic Bengali population of eastern India. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Department of Science & Technology, Govt. of India, under Cognitive Science Research Initiative Programme (DST/CSRI-PDF/2021/12) and (SR/CSRI/PDF-32/2014 and DST/CSRI-P/2017/22). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IPGME&R RESEARCH OVERSIGHT COMMITTEE AND APPROVED I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data described in this study are available from the corresponding author upon reasonable request.