Institute of Basic Medical Sciences, Neuroscience Center, National Human Brain Bank for Development and Function, Chinese Academy of Medical Sciences; Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, China.
J Alzheimers Dis. 2021;83(2):609-622. doi: 10.3233/JAD-210461.
Alzheimer's disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated.
To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination.
We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared.
The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples.
There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.
阿尔茨海默病（AD）是全球范围内导致负担日益加重的最具挑战性疾病之一。尽管 AD 的神经病理学诊断已经确立多年，但 AD 病理诊断样本中的代谢变化尚未得到充分研究。
阐明通过 AD 相关病理检查评估的尸检人脑样本中的潜在代谢失调。
我们对 44 个人脑组织进行了非靶向和靶向代谢组学分析。比较了 AD 组和对照组（NC）组海马体之间的代谢差异。
结果表明，包括苯丙氨酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成、生物素代谢和嘌呤代谢在内的普遍代谢失调与 AD 病理相关。靶向代谢组学显示，AD 样本中苯丙氨酸、苯丙酮酸和 N-乙酰-L-苯丙氨酸上调。此外，催化苯丙氨酸转化为苯丙酮酸的酶 IL-4I1 在 AD 样本中也上调。
AD 相关病理变化的海马体存在普遍的代谢失调。我们的研究表明，海马体中苯丙氨酸代谢失调可能是 AD 病理形成的重要发病机制。
