Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade.
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade.
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DOI：
10.1016/s1474-4422(09)70299-6
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发表时间：
2010-01
期刊：
影响因子：
48
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
Jack, Clifford R., Jr.;Knopman, David S.;Jagust, William J.;Shaw, Leslie M.;Aisen, Paul S.;Weiner, Michael W.;Petersen, Ronald C.;Trojanowski, John Q.
现有证据有力地支持阿尔茨海默病（AD）的起始事件与β-淀粉样蛋白（Aβ）肽的异常加工有关，最终导致脑中Aβ斑块的形成。这个过程发生在个体认知正常的时候。脑β淀粉样变性的生物标志物是CSF Aβ42减少和淀粉样蛋白PET示踪剂保留增加。经过一段时间的滞后期后，神经元功能障碍和神经变性成为主要的病理过程，这一滞后期因患者而异。神经元损伤和神经变性的生物标志物是CSF tau蛋白增加和脑萎缩的结构MRI测量。神经退行性变伴随着突触功能障碍，其通过PET上的氟脱氧葡萄糖摄取减少来指示。我们提出了一个将疾病阶段与AD生物标志物相关联的模型，其中Aβ生物标志物首先变得异常，然后是神经退行性生物标志物和认知症状，神经退行性生物标志物随后变得异常，并与临床症状严重程度相关。
Currently available evidence strongly supports the position that the initiating event in Alzheimer’s disease (AD) is related to abnormal processing of β-amyloid (Aβ) peptide, ultimately leading to formation of Aβ plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain β-amyloidosis are reductions in CSF Aβ42 and increased amyloid PET tracer retention. After a lag period, which varies from patient to patient, neuronal dysfunction and neurodegeneration become the dominant pathological processes. Biomarkers of neuronal injury and neurodegeneration are increased CSF tau and structural MRI measures of cerebral atrophy. Neurodegeneration is accompanied by synaptic dysfunction, which is indicated by decreased fluorodeoxyglucose uptake on PET. We propose a model that relates disease stage to AD biomarkers in which Aβ biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.