Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY, United States.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.
Int Rev Neurobiol. 2020;154:51-77. doi: 10.1016/bs.irn.2020.03.014. Epub 2020 Jul 10.
There is a vast literature linking systemic metabolic conditions to dementia due to Alzheimer's disease (AD). Advances in in vivo measurements of AD neuropathology using brain imaging, cerebrospinal fluid (CSF), and/or blood biomarkers have led to research in AD that uses in vivo biomarkers as outcomes, focusing primarily on amyloid, tau, and neurodegeneration as constructs. Studies of Type 2 Diabetes Mellitus (T2DM) and AD biomarkers seem to show that T2DM is not related to amyloid deposition, but is related to neurodegeneration and tau deposition. There is a dearth of studies examining adiposity, insulin resistance, and metabolic syndrome in relation to AD biomarkers and the associations in these studies are inconsistent. Metabolomics studies have reported associations of unsaturated fatty acids with AD neuropathology at autopsy, and sphingolipids and glycerophospholipids in relation to neurodegeneration and amyloid and tau. There are other neurodegenerative diseases, such as Lewy body disease that may overlap with AD, and specific biomarkers for these pathologies are being developed and should be integrated into AD biomarker research. More longitudinal studies are needed with concurrent assessment of metabolic factors and AD biomarkers in order to improve the opportunity to assess causality. Ideally, AD biomarkers should be integrated into clinical trials of interventions that affect metabolic factors. Advances in blood-based AD biomarkers, which are less costly and invasive compared with CSF and brain imaging biomarkers, could facilitate widespread implementation of AD biomarkers in studies examining the metabolic contribution to AD.
有大量文献将系统性代谢状况与阿尔茨海默病（AD）相关的痴呆联系起来。利用脑成像、脑脊液（CSF）和/或血液生物标志物对 AD 神经病理学进行体内测量的进展，促使 AD 研究采用体内生物标志物作为结果，主要集中在淀粉样蛋白、tau 和神经退行性变作为结构。2 型糖尿病（T2DM）和 AD 生物标志物的研究似乎表明，T2DM 与淀粉样蛋白沉积无关，而是与神经退行性变和 tau 沉积有关。很少有研究检查肥胖、胰岛素抵抗和代谢综合征与 AD 生物标志物的关系，而且这些研究的相关性不一致。代谢组学研究报告了在尸检中不饱和脂肪酸与 AD 神经病理学之间的关联，以及鞘脂和甘油磷脂与神经退行性变、淀粉样蛋白和 tau 之间的关联。还有其他神经退行性疾病，如路易体病，可能与 AD 重叠，针对这些病理学的特定生物标志物正在开发中，应该纳入 AD 生物标志物研究。为了提高评估因果关系的机会，需要进行更多具有代谢因素和 AD 生物标志物的纵向研究。理想情况下，AD 生物标志物应整合到影响代谢因素的干预临床试验中。与 CSF 和脑成像生物标志物相比，基于血液的 AD 生物标志物具有成本更低、侵入性更小的优势，这将有助于 AD 生物标志物在研究代谢对 AD 的贡献时广泛应用。
