Familial FTD in India

Abstract

AbstractBackgroundThe burden of dementia in India is estimated to increase by 197% by 2050, and Frontotemporal dementia (FTD) is among the leading causes of young‐onset dementia. With recent advances in molecular pathology, genetic mechanisms and emerging therapies in FTD, it is important to understand familial FTD patterns in the heterogeneous sociocultural context of India. High genetic diversity is characteristic of India, and its population bears genetic imprints of European, Asian and even African genomes. The objective of this presentation is to provide an account of FTD in India, with a focus on familial FTD and genetic mechanisms recently being identified.MethodThe prevalence of FTD in clinical dementia cohorts across different geographic regions in India, frequency of familial FTD, clinical presentations in the context of sociolinguistic and ethnic diversity, and genetic mechanisms are reported.ResultThe reported prevalence of FTD in clinical and research groups across India varies from 7% to 26%. The proportion of familial FTD ranges from 9.5% in Kolkata in the east, 15% in Trivandrum in the south, 24.6% from Hyderabad and more recently, as high as 40% in a recent study from Bangalore. Few genetic mutations were reported in early studies. In a recent large effort from Bangalore, India, 200 patients with FTD syndromes underwent three generation pedigree analysis, clinical and neuropsychological evaluation and MRI according to ADNI protocol. Nearly half underwent genetic analysis by next generation sequencing and RT‐PCR was done to analyse C9orf 11 in a subset. Novel gene mutations including SQSTM1, GRN, MAPT, PSEN2, TBK1 and C9orf were detected. Of these mutations, 11 were pathogenic in 11 and 26 were variants of unknown significance (VUS). Apart from abnormal protein accumulation due to MAPT and GRN, we also identified CSF1R, TREM2 and TYROBP, that are recognised as primary microgliopathies. A few examples of VUS include PRNP, LRRK2, GBA and PANK2 mutations.ConclusionResearch from familial FTD cohorts in India is contributing to growing evidence of a wider spectrum of genetic mechanisms for FTD. Our findings provide compelling evidence to increase harmonised global efforts to reduce risk and develop novel treatment strategies for FTD.