Hattapark Dejakaisaya1, Anna Harutyunyan2, Patrick Kwan3,4, Nigel C Jones5,6. 1. Department of Neuroscience, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, VIC, 3004, Australia. 2. Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Parkville, VIC, 3052, Australia. 3. Department of Neuroscience, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, VIC, 3004, Australia. patrick.kwan@monash.edu. 4. Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Parkville, VIC, 3052, Australia. patrick.kwan@monash.edu. 5. Department of Neuroscience, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, VIC, 3004, Australia. Nigel.Jones@monash.edu. 6. Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Parkville, VIC, 3052, Australia. Nigel.Jones@monash.edu.
Abstract
INTRODUCTION: The mechanistic role of amyloid precursor protein (APP) in Alzheimer's disease (AD) remains unclear. OBJECTIVES: Here, we aimed to identify alterations in cerebral metabolites and metabolic pathways in cortex, hippocampus and serum samples from Tg2576 mice, a widely used mouse model of AD. METHODS: Metabolomic profilings using liquid chromatography-mass spectrometry were performed and analysed with MetaboAnalyst and weighted correlation network analysis (WGCNA). RESULTS: Expressions of 11 metabolites in cortex, including hydroxyphenyllactate-linked to oxidative stress-and phosphatidylserine-lipid metabolism-were significantly different between Tg2576 and WT mice (false discovery rate < 0.05). Four metabolic pathways from cortex, including glycerophospholipid metabolism and pyrimidine metabolism, and one pathway (sulphur metabolism) from hippocampus, were significantly enriched in Tg2576 mice. Network analysis identified five pathways, including alanine, aspartate and glutamate metabolism, and mitochondria electron transport chain, that were significantly correlated with AD genotype. CONCLUSIONS: Changes in metabolite concentrations and metabolic pathways are present in the early stage of APP pathology, and may be important for AD development and progression.
INTRODUCTION: The mechanistic role of amyloid precursor protein (APP) in Alzheimer's disease (AD) remains unclear. OBJECTIVES: Here, we aimed to identify alterations in cerebral metabolites and metabolic pathways in cortex, hippocampus and serum samples from Tg2576 mice, a widely used mouse model of AD. METHODS: Metabolomic profilings using liquid chromatography-mass spectrometry were performed and analysed with MetaboAnalyst and weighted correlation network analysis (WGCNA). RESULTS: Expressions of 11 metabolites in cortex, including hydroxyphenyllactate-linked to oxidative stress-and phosphatidylserine-lipid metabolism-were significantly different between Tg2576 and WT mice (false discovery rate < 0.05). Four metabolic pathways from cortex, including glycerophospholipid metabolism and pyrimidine metabolism, and one pathway (sulphur metabolism) from hippocampus, were significantly enriched in Tg2576 mice. Network analysis identified five pathways, including alanine, aspartate and glutamate metabolism, and mitochondria electron transport chain, that were significantly correlated with AD genotype. CONCLUSIONS: Changes in metabolite concentrations and metabolic pathways are present in the early stage of APP pathology, and may be important for AD development and progression.
Authors: Anna Harutyunyan; Debbie Chong; Rui Li; Anup D Shah; Zahra Ali; Cheng Huang; Christopher K Barlow; Piero Perucca; Terence J O'Brien; Nigel C Jones; Ralf B Schittenhelm; Alison Anderson; Pablo M Casillas-Espinosa Journal: Int J Mol Sci Date: 2022-05-28 Impact factor: 6.208
Authors: Mona Khorani; Gerd Bobe; Donald G Matthews; Armando Alcazar Magana; Maya Caruso; Nora E Gray; Joseph F Quinn; Jan F Stevens; Amala Soumyanath; Claudia S Maier Journal: J Alzheimers Dis Date: 2022 Impact factor: 4.160
Authors: Alex B Speers; Manuel García-Jaramillo; Alicia Feryn; Donald G Matthews; Talia Lichtenberg; Maya Caruso; Kirsten M Wright; Joseph F Quinn; Jan F Stevens; Claudia S Maier; Amala Soumyanath; Nora E Gray Journal: Front Pharmacol Date: 2021-12-16 Impact factor: 5.810