The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration
NCT Number: NCT06490822
Acronym: PROTEINOSKIN
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Frontotemporal Lobar Degeneration
Interventions: PROCEDURE: Skin biopsy
Sponsor: Nantes University Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 80
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: OTHER
Start Date: 2024-08
Completion Date: 2027-12
Locations: Nantes University Hospital, Nantes, 44093, France

Summary:
Frontotemporal lobar degeneration (FTLD) is a clinically heterogeneous syndrome, characterized by progressive decline in behaviour and/or language. From a pathological standpoint, like the great majority of neurodegenerative disorders, FTLD are proteinopathies, which are characterized by the presence of specific protein deposits in the Central Nervous System (CNS). Accordingly, the two main deposits observed in FTLD are either made of Tau or transactive response DNA binding protein 43 (TDP-43).

In pathological conditions such as FTLD, both proteins are aggregated and hyperphosphorylated.

It is now well established that the pathological process in some proteinopathies such as synucleinopathies (of which Parkinson's disease is the main representative) is not limited to the brain but also widespread throughout the peripheral autonomic networks, including the autonomic innervation of the skin. In this context, many independent studies have shown that the pathological process in PD could be detected using routine punch skin biopsies opening the way for the development of original histopathological markers of the disease.

Our hypothesis is that such a scenario could also occur in FTLDs and that the detection of the pathological tau or TDP-43 protein in the skin could help in diagnosing FTLD. This is especially relevant as, despite the recent progress in genetics, neurobiology and neuroimaging, there are no available biomarkers for FTLD.

Primary Outcome Measures: Amount of TDP 43, assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin, Day of inclusion|Amount of Tau assessed by Western blot and qPCR, assessed by Western blot and qPCR to determine level of expression of Tau in the skin, Day of inclusion
Secondary Outcome Measures: Amount of Tau phosphorylation, phospho-tau/tau ratio in the skin will be measured by Western blot, Day of inclusion|Amount of TDP 43 phosphorylation, phospho-TDP-43 /TDP43 ratio in the skin will be measured by Western blot, Day of inclusion|Neuropsychological characterization, During their follow-up FTLD patients underwent a complete neuropsycological assessment define as:

* mini-mental state examination (MMSE)
* the 16-item Free Recall/Indicated Recall test (RL/RI-16 items)
* Rey figure and recall
* Trail Making Test (TMT A \& B)
* Wechsler Adult Intelligence Scale
* Literal (letter P) and categorical (animals) fluency
* Rapid Frontal Efficiency Battery (BREF)
* Wisconsin Card Sorting Test (WCST)
* Zoo test of Behavioural Assessment of the Dysexecutive Syndrome (BADS)
* Stroop test - 4 boards
* Oral image naming test (DO 80)
* Theory of mind (ToM-15)
* ekman facial emotion recognition test, day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS|Behaviour profile, The 10-items scale Daphne will be used to explore disinhibition (4 items), apathy(1 item), perseveration (1 item), hyperorality (2items), personal neglect (1 item) and loss of empathy (1 item), day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS|FTLD mutation, Mutation carrier patient will be identified among participant (not all the participant) who had a genetic screening had neen carried out during their follow up., before inclusion