This international observational study focuses on individuals with genetic forms of Frontotemporal Dementia and related disorders, including Progressive Supranuclear Palsy, Corticobasal Degeneration, and Amyotrophic Lateral Sclerosis[1]. The study aims to characterize phenotype-genotype correlations, develop biomarkers for genetic carriers, establish natural history data, and enable prevention trials[2].
Frontotemporal dementia (FTD) represents a group of clinically and genetically heterogeneous disorders characterized by progressive degeneration of the frontal and temporal lobes[3]. Approximately 20-30% of FTD cases have an autosomal dominant inheritance pattern, with mutations in several key genes identified[4].
| Parameter | Value |
|---|---|
| NCT Number | NCT05653778 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | FTD, PSP, CBS, ALS, Alzheimer's Disease |
| Sites | International |
Mutations in the MAPT (Microtubule-Associated Protein Tau) gene cause familial FTD, often with parkinsonism[5]:
Loss-of-function mutations in the GRN gene lead to haploinsufficiency[6]:
The hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of FTD and ALS[7]:
Genetic forms of FTD account for approximately 30-50% of all FTD cases. Unlike sporadic FTD, genetic forms offer unique opportunities for:
The study addresses how specific genetic mutations influence:
Phenotype-Genotype Correlation: Characterize how specific genetic mutations influence clinical presentation, disease progression, and imaging findings
Biomarker Development: Identify fluid and imaging biomarkers for:
Natural History Documentation: Establish comprehensive natural history data for each genetic subtype
Trial Readiness: Create infrastructure for preventive therapeutic trials in pre-symptomatic carriers
Neurological Examination
Cognitive Testing[8]
Behavioral Assessment
Structural Imaging
Functional Imaging
Genetic Testing
Fluid Analysis[9]
The most common FTD subtype[10]:
Language variants[11]:
Combination of:
Genetic forms often present with:
Genetic Status
Clinical Status
General Requirements
The study provides[12]:
The study enables:
Findings will inform:
The study complements other major FTD research initiatives:
Genetics of frontotemporal dementia: current understanding and future directions. Nature Reviews Neurology. 2024. ↩︎
Genetic frontotemporal dementia: a review of clinical features and disease mechanisms. Brain. 2022. ↩︎
Clinical features of frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry. 2021. ↩︎
The genetics of frontotemporal dementia. Handbook of Clinical Neurology. 2012. ↩︎
MAPT mutations in frontotemporal dementia and related disorders. Journal of Alzheimer's Disease. 2020. ↩︎
The genetics of frontotemporal dementia: a new player in the field. Lancet Neurology. 2013. ↩︎
C9orf72 repeat expansions: a decade of discoveries and remaining questions. Brain. 2023. ↩︎
Fluid biomarkers in frontotemporal dementia. Alzheimer's Research & Therapy. 2023. ↩︎
Biomarkers for genetic frontotemporal dementia. Journal of Neurology, Neurosurgery & Psychiatry. 2022. ↩︎
Diagnostic criteria for behavioral variant frontotemporal dementia. Brain. 2011. ↩︎
Classification and genetics of primary progressive aphasia. Nature Reviews Neurology. 2009. ↩︎
Clinical trials in genetic frontotemporal dementia: challenges and opportunities. Alzheimer's & Dementia. 2024. ↩︎