Frontotemporal Lobar Degeneration
Conditions
Keywords
FTLD, tau, TDP43, skin biopsy
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.
Interventions
PROCEDURESkin 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
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
(patients): * 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 * Membership of social security scheme Inclusion Criteria (healthy volunteers): * No history of neurological disease, diabetes, or alteration/damage of peripheral nervous system * Aged 50-75 years Paired to at least one patient on age (less or more 5 years) * MOCA ≥ 26 * Membership of social security scheme Non inclusion Criteria (Patients and healthy volunteers): * Concomitting conditions affecting the peripheral nervous system such as but not limited to diabetes, renal failure, thyroid disorder, vitamin B12 deficiency, acute and chronic inflammatory diseases HIV, syphilis * Know allergy to local anesthetic * Known coagulopathy * Pregnant women or breastfeeding women * Person under court protection sous sauvegarde de justice * Person under guardianship * Inability to sign an informed consent Non inclusion criteria (Patients) • Patient with neurological disease other than FTLD Non inclusion criteria (Healthy volunteers) : • Evidence of neurological disorder at the inclusion including but not limted to FTLD, Parkinson disease, Alzheimer disease, lewy body dementia, Huntington disease, systemic lupus erythematosus multiple sclerosis; learning disabilities, mental retardation, severe hypoxic brain injuries, brain trauma with permanent cognitive impairments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of TDP 43 | Day of inclusion | 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 | Day of inclusion | assessed by Western blot and qPCR to determine level of expression of Tau in the skin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 test |
| Amount of Tau phosphorylation | Day of inclusion | phospho-tau/tau 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. |
| 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) |
| Amount of TDP 43 phosphorylation | Day of inclusion | phospho-TDP-43 /TDP43 ratio in the skin will be measured by Western blot |
Countries
France
Contacts
Primary ContactClaire BOUTOLEAU-BRETONNIERE, MD
Backup Contactpascal DERKINDEREN, Pr
Outcome results
None listed