Deep phenotyping and genotypic risk in presymptomatic family members of frontotemporal dementia patients in india (D-PRIME-FTD) project summary/abstract frontotemporal dementia (FTD) is a…

The National Institute on Aging awarded the National Institute of Mental Health and Neuro Sciences $215,961 on September 1, 2026, under the Aging Research program (CFDA 93.866) to establish and characterize a cohort of 300 presymptomatic family members of frontotemporal dementia patients in India through deep phenotyping, genetic profiling, serum biomarkers, and advanced brain imaging. The work aims to identify early indicators of disease progression in presymptomatic relatives carrying mutations in C9ORF72, GRN, and MAPT genes, stratify individuals by genetic risk and presymptomatic status, and enhance clinical trial readiness for targeted therapies and biomarker-driven interventions in a population underrepresented in frontotemporal lobar degeneration research. Place of performance is India, with a project period from September 1, 2026, through August 31, 2028.

Deep phenotyping and genotypic risk in presymptomatic family members of frontotemporal dementia patients in india (D-PRIME-FTD) project summary/abstract frontotemporal dementia (FTD) is a neurodegenerative disorder marked by behavioral, language, and motor changes, associated with degeneration of frontal and temporal lobes, [frontotemporal lobar degeneration (FTLD)]. Its presentation often overlaps with symptoms seen in psychiatric conditions. FTLD is highly heritable, with 20% linked to mutations in C9ORF72, GRN and mapt genes. Early identification of FTLD is crucial for clinical trials targeting preclinical stages, where subtle cognitive and behavioral changes, alongside biomarkers such as brain volumes, and neurofilament light chain (NFL), precede symptoms. India's diverse population offers a unique opportunity to expand FTLD research and enhance global trial readiness. Familial forms of FTLD, which account for up to 40% of cases, provide an opportunity to study early disease mechanisms through clinical and genetic profiling. While large multinational studies have characterized presymptomatic FTLD in western populations, there is a critical GAP in understanding its trajectory in diverse populations like india. This proposed study aims to establish a group of well-characterized high-risk presymptomatic relatives of FTLD families in india, using deep phenotyping, genetics, serum biomarkers, and advanced brain imaging. By identifying these multimodal markers in ≈300 presymptomatic family members, we will unravel early indicators of disease progression and stratify individuals based on genetic risk and presymptomatic status. This comprehensive approach will provide insights into the disease trajectory, and enhance clinical trial readiness, contributing to the development of targeted therapies and biomarker-driven interventions for FTLD in the indian populations.