Heritability in frontotemporal dementia: more missing pieces?

Area of Science:

• Neuroscience
• Genetics
• Dementia Research

Background:

• Frontotemporal dementia (FTD) is recognized as highly heritable, yet specific genetic causes are frequently unidentified.
• This discrepancy necessitates further investigation into the genetic underpinnings and family history patterns of FTD.

Purpose of the Study:

• To investigate the
• strength
• of family history in Frontotemporal dementia (FTD) compared to Alzheimer's disease (AD) and controls.
• To examine clinical syndromes associated with FTD and AD heritability.
• To identify genetic causes in a subset of FTD patients.

Main Methods:

• Recruited 122 FTD patients, 98 AD patients, and 87 controls from an FTD research clinic.
• Assessed family history strength using the Goldman score (GS), with GS 1-3 indicating a
• strong
• family history.
• Screened a subset of FTD patients for known genetic mutations (C9ORF72, GRN, MAPT).

Main Results:

• A strong family history was significantly more prevalent in FTD (17.2%) than in AD (5.1%) and controls (2.3%).
• Behavioral variant FTD (bvFTD) and FTD-ALS subgroups were key drivers of FTD heritability.
• Pathogenic mutations were found in 16 FTD patients, but over half of FTD cases with a strong family history lacked identified mutations.

Conclusions:

• FTD demonstrates higher heritability than AD, with bvFTD and FTD-ALS significantly contributing.
• Atypical AD also appears more heritable than typical AD.
• The findings indicate that additional, yet undiscovered, genetic factors likely influence FTD development.