Targeted Serum Metabolite Profiling Identifies Metabolic Signatures in Patients with Alzheimer's Disease, Normal Pressure Hydrocephalus and Brain Tumor
Article
This work was funded by the Karen L. Wrenn Estate (Majorie B. Thomas Trustee) under the Florida Hospital Foundation. The authors thank to Anette Untermann for technical assistance in metabolomics analysis, Sajeel Chowdhary, MD, Philip St. Louis MD, and Dr. Nikhil Rao for their support in patient selection, and Sergay Bushnev and Julie Pepe, Ph.D. for their participation in protocol development.
abstract
Progression to AD is preceded by elevated levels of 2,4-dihydroxybutanoic acid (2,4-DHB), implicating hypoxia in early pathogenesis. Since hypoxia may play a role in multiple CNS disorders, we investigated serummetabolite profiles across three disorders, AD, Normal Pressure Hydrocephalus (NPH) and brain tumors (BT). Blood samples were collected from 27 NPH and 20 BT patients. The profiles of 21 metabolites were examined. Additionally, data from 37 AD patients and 46 controls from a previous study were analyzed together with the newly acquired data. No differences in 2,4-DHB were found across AD, NPH and BT samples. In the BT group, the fatty acids were increased as compared to HC and NPH groups, while the ketone body 3-hydroxybutyrate was increased as compared to AD. Glutamic acid was increased in AD as compared to the HC group. In the AD group, 3-hydroxybutyrate tended to be decreased with respect to all other groups (mean values -30% or more), but the differences were not statistically significant. Serine was increased in NPH as compared to BT. In conclusion, AD, NPH and BT have different metabolic profiles. This preliminary study may help in identifying the blood based markers that are specific to these three CNS diseases.