The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration
- Conditions
- Frontotemporal Lobar Degeneration
- Interventions
- Procedure: Skin biopsy
- Registration Number
- NCT06490822
- Lead Sponsor
- Nantes University Hospital
- Brief 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.
- Detailed Description
Participant with Frontotemporal Lobar degeneration equally distributed into behavioral variant of frontotemporal dementia (bvFTD), language variant with primary progressive aphasia (PPA) and motor presentations with atypical parkinsonian disorders (corticobasal degeneration-CBD and progressive supranuclear palsy-PSP) and motoneuron disorder (amyotrophic lateral sclerosis -ALS) will be included at Nantes University Hospital during a period of 24 months.
Healthy volunteers will be included as comparative group. A skin biopsy and venous blood samples will be collected for all participants.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single arm study Skin biopsy A single 3 mm-diameter punch skin biopsy will be obtained from FTLD patients and healthy volunteers at the C8 paravertebral under local anesthesia to analyze cutaneous innervation
- Primary Outcome Measures
Name Time Method Amount of Tau assessed by Western blot and qPCR Day of inclusion assessed by Western blot and qPCR to determine level of expression of Tau in the skin
Amount of TDP 43 Day of inclusion assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin
- Secondary Outcome Measures
Name Time Method Amount of TDP 43 phosphorylation Day of inclusion phospho-TDP-43 /TDP43 ratio in the skin will be measured by Western blot
FTLD mutation before inclusion 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.
Neuropsychological characterization day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS 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 testAmount of Tau phosphorylation Day of inclusion phospho-tau/tau ratio in the skin will be measured by Western blot
Behaviour profile day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS 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)
Trial Locations
- Locations (1)
Nantes University Hospital
🇫🇷Nantes, France