Not Just Alzheimer’s: An Inflammatory and Biomolecular Profile of Frontotemporal Dementia Identified

Frontotemporal Dementia is a form of dementia with an often presenile onset, characterized by behavioral and language disorders. Several cases are transmitted across generations and have a genetic cause, meaning that patients are carriers of mutations in specific genes. The advantage of studying individuals—both affected and unaffected—from families where the disease recurs, is the possibility to study the early stages of the disease and identify specific profiles that have the potential to predict the course, as well as helping us better understand the mechanisms underlying the disease, which are still poorly understood today.

Thanks to an international collaboration, the “Genetic Frontotemporal dementia Initiative” (GENFI) consortium was established for the study of these cases (https://www.genfi.org/), in which our Center also participates.

To date, more than 1,000 subjects belonging to these families have been included, both symptomatic and non-symptomatic, from whom blood samples have been collected. On the latter, we evaluated the profile of inflammatory molecules and other molecules that regulate gene expression, identifying specific profiles in patients compared to healthy subjects. Furthermore, carriers of disease-causing mutations who did not yet manifest symptoms were studied; it was observed that one of these inflammatory factors is already altered in the presymptomatic phase and is therefore a very early event in the development of the disease.

These studies demonstrate how inflammation and the alteration of regulatory factors of gene expression are involved in the pathogenesis of Frontotemporal Dementia and may represent new therapeutic targets for the development of drugs that can prevent or delay the development of the disease.