Frontotemporal Dementia (FTD) is a severe and currently incurable neurodegenerative disease that significantly impacts the lives of aging individuals. This disease is characterized by a variety of debilitating symptoms including personality changes, motor deficits, and cognitive impairments. Recent research has highlighted the role of a specific form of the tau protein, known as cis P-tau, in the progression of several neurodegenerative diseases. However, the involvement of cis P-tau in FTD has not yet been investigated.

Our research aims to determine the role of cis P-tau in FTD and explore the potential of a novel therapeutic approach using a monoclonal antibody (cis mAb) that targets cis P-tau. Preliminary studies have shown that cis P-tau is present in FTD patients and mouse models, suggesting it plays a role in the disease’s pathology. We have demonstrated that treating FTD mouse models with cis mAb significantly reduces cis P-tau and associated gliosis, a type of brain inflammation.

This project seeks to extend these findings by evaluating the efficacy of cis mAb in preventing the progression of FTD symptoms and pathology in two complementary mouse models. We will assess the ability of cis mAb to reduce tau pathology, neuronal loss, and gliosis, as well as its impact on behavioral deficits such as disinhibition, memory impairment, and motor dysfunction. Furthermore, we will utilize advanced single-nucleus RNA sequencing to understand how cis mAb affects cell type-specific transcriptomic changes in the brain.

Our interdisciplinary team, consisting of experts in neurology, pathology, mouse behaviors, statistics and bioinformatics, is uniquely positioned to carry out this research. This study holds the promise of developing a targeted therapy for FTD, potentially transforming the lives of those affected by this devastating disease