Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings

被引:33
作者
Blennow, Kaj [1 ,2 ]
Zetterberg, Henrik [1 ,2 ,3 ,4 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
[2] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
[3] UCL, UK Dementia Res Inst, London, England
[4] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England
来源
MOLECULAR BIOLOGY OF NEURODEGENERATIVE DISEASES: VISIONS FOR THE FUTURE, PT A | 2019年 / 168卷
关键词
HUMAN CEREBROSPINAL-FLUID; NEUROFILAMENT LIGHT-CHAIN; MILD COGNITIVE IMPAIRMENT; CREUTZFELDT-JAKOB-DISEASE; PROTEIN-KINASE-C; AGED HUMAN BRAIN; BETA-AMYLOID; 42; CSF BIOMARKERS; NEUROFIBRILLARY TANGLES; PHOSPHO-TAU;
D O I
10.1016/bs.pmbts.2019.07.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease (AD) is very difficult to diagnose on pure clinical grounds, especially in the earlier phases of the disease. At the same time, lessons from recent clinical trials suggest that treatments have to be initiated very early, to have a chance to show clinical efficacy. Therefore, biomarkers reflecting core AD pathophysiology have a key position in clinical trials and clinical management. The core AD cerebrospinal fluid (CSF) biomarker toolbox include amyloid beta (A beta 42 and the A beta 42/40 ratio) reflecting brain amyloidosis, total tau (T-tau) reflecting neurodegeneration intensity, and phosphorylated tau (P-tau) that is related to tau pathology. These CSF biomarkers have very consistently been found to have high diagnostic accuracy, also in earlier disease stages. Importantly, CSF A beta 42 and A beta 42/40 ratio show excellent agreement with amyloid PET readouts, indicating that these biomarker tests can be used interchangeably. Intense collaborative standardization efforts have given Certified Reference Materials (CRMs) to harmonize assay formats for CSF A beta 42, the most central AD biomarker, and CRMs for A beta 40 are under development. The core AD biomarkers are today available on high-precision fully automated analytical platforms, which will serve to introduce uniform cut-off levels and enable the large-scale introduction of CSF biomarkers for routine disease diagnosis. Of novel biomarker candidates, synaptic proteins, such as the dendritic protein neurogranin, show promise as tools to monitor synaptic degeneration, an important aspect of AD pathophysiology. Recent studies show that the core AD biomarkers also can be measured in blood samples. Ultra-sensitive assays that allow for quantification of neuronal proteins, such as tau and neurofilament light (NFL) in blood samples. Further, plasma A beta 42 and A beta 42/40 show high concordance with brain amyloidosis evaluated by PET scans. In the future, blood biomarkers may have value as screening tools, especially to rule out patients without biomarker evidence of AD pathology.
引用
收藏
页码:3 / 23
页数:21
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