Janani Parameswaran, PhD

2025 Next Generation Research Grant in FTD

The Role of Protein Fibrils in ALS/FTD

Institution: Emory University

Project Summary:

Frontotemporal dementia (FTD) is a neurodegenerative disorder that shares some genetic characteristics with amyotrophic later sclerosis (ALS). A key feature shared by various neurodegenerative diseases is the clumping of proteins in and around neurons and glial support cells. These include tau, amyloid-β, α-synuclein, TDP-43, and poly-glutamine. Recent studies have also revealed the presence of groups, called fibrils, of transmembrane protein 106B (TMEM106B) in a specific genetic variant of FTD and ALS called C9orf72, as well as in healthy older individuals. However, we don’t know how or even if these fibrils influence the development and progression of neurodegeneration.

Dr. Parameswaran plans to study the role of TMEM106B fibrils and how they might contribute to neurodegeneration and cognitive decline. She also will investigate how they affect which genes are activated or suppressed during the process of making proteins. If TMEM106B fibrils do play a significant role in neurodegeneration or cognitive decline, understanding these signaling pathways could open avenues for targeted therapies.

This research is funded by The Holloway Family Fund at The Association for Frontotemporal Degeneration and the American Brain Foundation, in collaboration with the American Academy of Neurology.