title: Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome.
abstract: The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Pan
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Muhammad Bin
authors.initials: MB
authors.lastname: Nasaruddin
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Elliott
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Bernadette
authors.initials: B
authors.lastname: McGuinness
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Passmore
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine, UK.
authors.forename: Paula L
authors.initials: PL
authors.lastname: McClean
authors.affiliation: Beaumont Research Institute, Royal Oak, MI, USA.
authors.forename: Stewart F
authors.initials: SF
authors.lastname: Graham
authors.affiliation: Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland, UK. Electronic address: b.green@qub.ac.uk.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
mesh_terms: D000375:Aging / Q000097:blood / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000378:metabolism; D000601:Amino Acids, Essential / Q000097:blood / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000097:blood* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D055442:Metabolome; D008822:Mice, Transgenic; D010743:Phospholipids / Q000097:blood / Q000378:metabolism; D012701:Serotonin / Q000097:blood / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D000601:Amino Acids, Essential; D015317:Biogenic Polyamines; D010743:Phospholipids; C116917:acylcarnitine; D012701:Serotonin; D002331:Carnitine
keywords: APP/PS1; Alzheimer's disease; Blood; Brain; Metabolites; Metabolomics