Plasma Abeta Peptides and the Risk of Alzheimer's Disease. Diagnostic Performance and Predictive and Prognostic Values of Measurements of Plasma Amyloid Peptides Concentrations for the Diagnosis of Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,067
- 试验地点
- 1
- 主要终点
- plasma levels of Tau protein
研究概览
简要总结
The aim of this study is to examine the relationship between plasma putative biomarkers for Alzheimer's disease (i.e. Ab40 amyloid and total Ab42 amyloid, free, bound, free/bound, truncated, sAPPα) and :
- the risk of conversion of individuals with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD),
- the Alzheimer's disease progression rate.
详细描述
Rational Whether there are biological markers of Alzheimer's disease (AD) is crucial for adequate targeting and appropriate management of the disease. The aim of our study is to examine diagnostic performance and predictive and prognostic values of new plasma markers of AD.
Results of studies on the predictive value of plasma concentrations of Aβ40 and 42 amyloid peptides for incident AD are not straightforward. Discrepancies in these results may be due to the fact that total peptide concentrations have been measured. One recent study suggests that plasma free Aβ peptide concentration and particularly low-density lipoprotein receptor-related protein (LPR) as like as free Aβ/total Aβ ratio would be more reliable and discriminant.
Main objective of the study To examine the association between plasma free Aβ peptide concentration and (1) the risk of conversion of subjects with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD) and (2) the risk of worsening of the disease in patients with mild and moderate stages of AD.
Secondary objectives
- To examine the association of total peptid Aβ concentration, free Aβ/Total Aβ ratio, and trunked plasmatic Aβ to the risk of incident AD in MCI subjects, and to the risk of worsening of the disease in mild and moderate AD patients,
- To examine the association between serum sAPP concentration and the risk of incident AD in MCI subjects, and the risk of worsening of the disease in mild and moderate AD patients,
- To compare the time evolution of concentrations of these biomarkers to Alzheimer's disease progression rate which will be assessed on the basis of neuropsychological examinations and MRI examination of hippocampal atrophy,
- To examine the association between serum and cerebrospinal fluid (CSF) concentrations of AD biomarkers in subgroup of participants who undergo lumbar puncture,
- To examine the association between neuroimaging data (cerebral volume, hippocampal volume, cerebrovascular lesions and plasma and CSF AD biomarkers' concentrations,
- To constitute blood and plasma banks, gene bank and CSF bank for future studies on other biomarkers of AD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MCI group :
- •≥ 70 years
- •MCI diagnosis : New criteria (Petersen, PORTET*)
- •cognitive complaint from the patient, family, or both,
- •report by the subject or reporter of a decline in cognitive or functional performance, relative to previous abilities,
- •cognitive disorders evidenced by clinical evaluation: impairment in memory or another cognitive domain,
- •cognitive impairment without any repercussion on daily life, even if the subject reports difficulties concerning complex daily activities,
- •no dementia
- •Having signed an informed consent form
- •Fluent in French
- •≥ 45 years
- •AD diagnosis (DSM IV-TR et NINCDS-ADRDA)
- •Mild to moderate (MMSE > 15)
- •Having signed an informed consent form
- •Caregiver/informant to provide information on patient
排除标准
- •Normal cognitive function
- •Major depression (according to the DSMIV-TR or MINI or Geriatric depression Scale> 20/30)
- •Genetic form of AD (genetic mutation known)
- •All other diseases that could interfere with cognitive assessment (Epilepsy, Parkinson's disease, schizophrenia, other dementia)
- •Major sensory deficits that could interfere with cognitive assessment (visual and auditory)
- •Diseases involving the short-term survival (advanced cancer, unstable heart disease, severe hepatic/respiratory/renal failure)
- •Contraindication for MRI, for lumbar puncture (i.e. anticoagulant agents)
- •Use of any experimental agent for the duration of the study
- •Participation to other biomedical research that could interfere with principal objective of the study
- •For MCI patient, use of IchE or memantine medication before inclusion
- •Less than 4 years of education
- •Illiteracy, is unable to count or to read
- •Pregnant women
- •Non health insurance affiliation
- •Private subjects of freedom by legal or administrative decision
- •Contraindication for MRI examination:
- •Claustrophobic subject
- •Carrying a cardiac pacemaker
- •Presence of any ferromagnetic metallic implants or foreign bodies (carrying an internal electrical/magnetic device, carrying a valvular prosthesis)
- •Carrying a ventricular valvular
- •Exclusion criteria specific to the lumbar puncture:
- •Taking anticoagulant agents
研究组 & 干预措施
biomarkers, MRI and CSF
Longitudinal multicenter study including 1300 subjects with amnestic impairment (MCI, n=650 and AD, n=650) derived from the main French national Memory Resources and Research Centers.
Participants will undergo at baseline and every 6 months a neurological examination, a neuropsychological assessment (and an oculomotor examination for those included from Broca Hospital).
Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study (or the conversion).
干预措施: biomarkers, MRI and CSF (Biological)
结局指标
主要结局
plasma levels of Tau protein
时间窗: t0
Ancillary study :comparison of plasma levels of Tau protein at baseline between MCI converters and MCI non-converters and between rapidly and non-rapidly progressing AD.
Mean concentration of plasma AB peptides
时间窗: at t0 and 24 months
* MCI "converted" (MCI-AD) * and stable MCI (MCI-MCI) groups
次要结局
- MRI(T0 + M24 or conversion)
- Transcriptomics biomarkers(T0 and 24 months or conversions)
- TACE/ADAM17(to)
- sAPPβ(t0)
- Ratio of CSF sAPPβ and CSF sAPPα(t0)
- Ratio of plasma Aβ and plasma Tau(t0)
- Cathepsin(t0)
- Bace peptide(t0)
- Plasma Tau(24 months)
- MRI biomarkers(24 months)
- Mean concentration of biomarker(t0 and 24 months)