Presymptomatic studies in genetic frontotemporal dementia.

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• Frontotemporal dementia (FTD) is a neurodegenerative disorder with a significant genetic component, often inherited in an autosomal dominant pattern.
• Mutations in progranulin (GRN), microtubule-associated protein tau (MAPT), and chromosome 9 open reading frame 72 (C9orf72) are the most common genetic causes of FTD.

Purpose of the Study:

• To investigate the preclinical and prodromal stages of genetic FTD.
• To identify the sequence and timing of biomarker and neuroimaging changes preceding symptom onset in genetic FTD.

Main Methods:

• Longitudinal studies tracking plasma biomarkers, MR imaging (functional and structural connectivity), and grey matter atrophy.
• Analysis of presymptomatic changes in individuals with genetic FTD.

Main Results:

• Evidence suggests a temporal sequence of presymptomatic changes in genetic FTD, beginning with alterations in plasma biomarkers.
• These are followed by abnormalities in MR imaging related to functional and structural connectivity, and subsequently grey matter atrophy.
• Neuropsychometric test abnormalities appear closer to symptom onset.

Conclusions:

• Understanding the presymptomatic trajectory of genetic FTD is crucial for early detection and intervention.
• The formation of large consortia like the Genetic Frontotemporal Dementia Initiative (GenFI) is essential for accumulating sufficient data for future clinical trials.