Review: Modelling the pathology and behaviour of frontotemporal dementia

Area of Science:

• Neuroscience
• Genetics
• Neuropathology

Background:

• Frontotemporal dementia (FTD) is a group of neurological disorders characterized by behavioral and language dysfunction.
• Neurodegeneration in the frontal and temporal cortices is a hallmark of FTD.
• Advances in genetics and neuropathology have spurred the development of FTD disease models.

Purpose of the Study:

• To review in vivo model systems for studying FTD pathomechanisms.
• To focus on models that reproduce FTD's behavioral phenotypes.
• To discuss emerging disease pathways and challenges in FTD modeling.

Main Methods:

• Generation of in vivo models by targeting genes (GRN, C9orf72) or proteins (TDP-43, FUS).
• Analysis of behavioral phenotypes in FTD models.
• Review of existing literature on FTD in vivo models.

Main Results:

• In vivo models replicate key pathological and behavioral aspects of FTD.
• These models have illuminated emerging disease pathways.
• Challenges remain in fully capturing the complexity of FTD symptoms and overlap with motor neuron disease.

Conclusions:

• In vivo models are valuable tools for understanding FTD pathogenesis.
• Further refinement and comparative analysis of models are needed to enhance disease relevance.
• Improved model systems will better inform therapeutic development for FTD.