The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Amount of Tau assessed by Western blot and qPCR
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(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.
排除标准
- 未提供
研究组 & 干预措施
Single arm study
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
干预措施: Skin biopsy (Procedure)
结局指标
主要结局
Amount of Tau assessed by Western blot and qPCR
时间窗: Day of inclusion
assessed by Western blot and qPCR to determine level of expression of Tau in the skin
Amount of TDP 43
时间窗: Day of inclusion
assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin
次要结局
- Amount of TDP 43 phosphorylation(Day of inclusion)
- FTLD mutation(before inclusion)
- 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)
- Amount of Tau phosphorylation(Day of inclusion)
- 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)