Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome

Xiaobei Pan, Muhammad Bin Nasaruddin, Christopher T. Elliott, Bernadette McGuinness, Anthony P. Passmore, Patrick G Kehoe, Christian Holscher, Paula L. McClean, Stewart F. Graham, Brian D. Green

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Abstract

The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon 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 APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT 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 was evident in two age groups. AD-like pathology therefore impacts 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.
Original languageEnglish
Pages (from-to)151-163
Number of pages13
JournalNeurobiology of Aging
Volume38
Early online date30 Nov 2015
DOIs
Publication statusPublished - Feb 2016

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