关键词: Alzheimer’s disease Amyloid beta Amyloidosis Biomarker Blood Plasma

Mesh : Humans Alzheimer Disease / diagnostic imaging Amyloid beta-Peptides / cerebrospinal fluid Plaque, Amyloid / diagnostic imaging Peptide Fragments / cerebrospinal fluid Brain / diagnostic imaging metabolism Amyloid Amyloidogenic Proteins Biomarkers / cerebrospinal fluid Positron-Emission Tomography / methods

来  源:   DOI:10.1186/s13195-022-01117-1   PDF(Pubmed)

Abstract:
The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark of Alzheimer\'s disease (AD). Detection of Aβ pathology is essential for AD diagnosis and for identifying and recruiting research participants for clinical trials evaluating disease-modifying therapies. Currently, AD diagnoses are usually made by clinical assessments, although detection of AD pathology with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used by specialty clinics. These measures of Aβ aggregation, e.g. plaques, protofibrils, and oligomers, are medically invasive and often only available at specialized medical centers or not covered by medical insurance, and PET scans are costly. Therefore, a major goal in recent years has been to identify blood-based biomarkers that can accurately detect AD pathology with cost-effective, minimally invasive procedures.To assess the performance of plasma Aβ assays in predicting amyloid burden in the central nervous system (CNS), this review compares twenty-one different manuscripts that used measurements of 42 and 40 amino acid-long Aβ (Aβ42 and Aβ40) in plasma to predict CNS amyloid status. Methodologies that quantitate Aβ42 and 40 peptides in blood via immunoassay or immunoprecipitation-mass spectrometry (IP-MS) were considered, and their ability to distinguish participants with amyloidosis compared to amyloid PET and CSF Aβ measures as reference standards was evaluated. Recent studies indicate that some IP-MS assays perform well in accurately and precisely measuring Aβ and detecting brain amyloid aggregates.
摘要:
脑中淀粉样β(Aβ)斑块的细胞外积累是阿尔茨海默病(AD)的标志。Aβ病理学的检测对于AD诊断以及识别和招募研究参与者用于评估疾病改善疗法的临床试验至关重要。目前,AD诊断通常通过临床评估来进行,尽管通过正电子发射断层扫描(PET)扫描或脑脊液(CSF)分析检测AD病理可用于专科诊所。这些Aβ聚集的测量,例如,斑块,原纤维,和低聚物,具有医疗侵入性,通常仅在专业医疗中心提供或不在医疗保险范围内,和PET扫描是昂贵的。因此,近年来的一个主要目标是鉴定基于血液的生物标志物,这些生物标志物可以准确地检测出具有成本效益的AD病理,微创手术。为了评估血浆Aβ测定在预测中枢神经系统(CNS)淀粉样蛋白负荷中的性能,这篇综述比较了21篇不同的手稿,这些手稿使用血浆中42和40个氨基酸长的Aβ(Aβ42和Aβ40)的测量来预测CNS淀粉样蛋白状态.考虑了通过免疫测定或免疫沉淀-质谱(IP-MS)定量血液中Aβ42和40肽的方法,与作为参考标准的淀粉样蛋白PET和CSFAβ测量相比,评估了他们区分淀粉样变性参与者的能力.最近的研究表明,一些IP-MS测定法在准确和精确地测量Aβ和检测脑淀粉样蛋白聚集体方面表现良好。
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