Research on FTLD may deal with cortical lesions responsible for dementia or with motor neuron changes (responsible for amyotrophic lateral sclerosis). It makes use of animal models such as transgenic mouse lines carrying mutations of Tau protein gene. However, Tau accumulation is found in less than 40% of FTLDs. Other accumulated proteins or altered genetic pathways were identified only by studies of human diseases.
Why is research on post mortem human nervous tissue still useful ?
1. The observation of diseased human tissues makes it possible to identify hitherto undescribed lesions and to develop hypotheses.
2. The mechanism of neuron degeneration in FTLD is still imperfectly known. Regional vulnerabilty is not completely understood. TDP-43 protein is one of the main constituents of the lesions in many cases, but other molecules, maybe crucial for the development of the disease, have also been found in the lesions or remain to be discovered.
3. All the models are incomplete. The analysis of human tissues remain essential and has to be confronted with the data obtained from experimental models.
4.
To evaluate whether new therapeutic attempts modify the lesions and their progression in the nervous system, it will be essential to compare well-documented samples with or without treatment.