Introduction: AD is the most complex disorder leading to dementia worldwide. Despite the disease burden among Indians the mutation spectrum in our subcontinent is not well examined. Methods: To identify probable causal variants for AD, in a total of 29 clinically diagnosed, majorly familial and young onset AD cases from Eastern India, whole exome analysis in Illumina NovoSeq. 6000 sequencing platform was performed as per standard methodology. Next, the coding variants were prioritised based on the literature and our bioinformatic analyses for genotype-to-phenotype correlation. Results: A total of 25 missense variants and 4 nonsense variants in 17 genes among 23 AD cases were identified as probable damaging ones in our study cohort. Amongst all, ABCA7 account for the maximum number of pathogenic variants (5/29). A lowering in the age of onset was observed for mutation carriers and cases belonging to the posterior cortical atrophy (PCA) subgroup. Our further comparative analyses suggested that variants in APP metabolism pathway genes are more common in PCA, frontal AD, and young-onset multi-domain amnestic phenotypes than dysexecutive and typical AD. Conclusion Our study suggests that whole exome sequencing among Indian AD patients holds the potential to identify the most common gene as well as clinically relevant new causal variants which may highlight new insight into disease mechanism through future research.

The authors have declared no competing interest.

Supported by grants from the Department of Science & Technology, Govt. of India, under the Cognitive Science Research Initiative Programme (DST/CSRI-P/2017/22), and Department of Biotechnology, Ministry of Science & Technology, Govt. of India (BT/NIDAN/01/05/2018).

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the IPGME&R, Kolkata, and National Neurosciences Centre Calcutta, Kolkata, India. The Ethics Committees (Institutional Ethics Committee, IPGME&R, Kolkata and National Neurosciences Centre Calcutta, Kolkata) of the abovementioned Institutes approved the study protocol. Informed consent was taken as per guidelines of the Indian Council of Medical Research, National Ethical Guidelines for Biomedical and Health Research involving human participants, India.

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