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.
Adressed or followed at memory clinic or ALS expert center at Nantes university hospital.
Aged 50-75 years
Fulfilling current diagnosis criteria for one of the disorder: vcfFTD, non-Alzheimer PPA (semantic or non fluent), DCB or PSP,ALS
MMSE ≥ 18
None
Single group
Skin biopsy
Procedure/SurgeryA 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
Amount of TDP 43
assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin
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
Amount of Tau phosphorylation
phospho-tau/tau ratio in the skin will be measured by Western blot
Amount of TDP 43 phosphorylation
phospho-TDP-43 /TDP43 ratio in the skin will be measured by Western blot
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
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)
Click on the lead sponsor to view all of their trials.
