Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA. jack.cliff
Lancet Neurol. 2010 Jan;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6.
Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of beta-amyloid (Abeta) peptide, ultimately leading to formation of Abeta plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain beta-amyloidosis are reductions in CSF Abeta(42) 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 Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.
目前的证据有力地支持了阿尔茨海默病（AD）的起始事件与β-淀粉样蛋白（Abeta）肽的异常处理有关这一观点，最终导致大脑中 Abeta 斑块的形成。这一过程发生在个体认知功能仍正常的时候。脑β-淀粉样蛋白病的生物标志物是 CSF Abeta（42）减少和淀粉样蛋白 PET 示踪剂保留增加。在从患者到患者的时间滞后之后，神经元功能障碍和神经退行性变成为主要的病理过程。神经元损伤和神经退行性变的生物标志物是 CSF tau 增加和脑萎缩的结构 MRI 测量值。神经退行性变伴随着突触功能障碍，这表现在 PET 上的氟脱氧葡萄糖摄取减少。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 Abeta 生物标志物首先出现异常，然后是神经退行性生物标志物和认知症状，而神经退行性生物标志物出现异常较晚，并与临床症状严重程度相关。
