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

被引：96

作者：

Pan, Xiaobei ^{[1
]}

Bin Nasaruddin, Muhammad ^{[1
]}

Elliott, Christopher T. ^{[1
]}

McGuinness, Bernadette ^{[2
]}

Passmore, Anthony P. ^{[2
]}

Kehoe, Patrick G. ^{[3
]}

Hoelscher, Christian ^{[4
]}

McClean, Paula L. ^{[5
]}

Graham, Stewart F. ^{[6
]}

Green, Brian D. ^{[1
]}

机构：

[1] Queens Univ Belfast, Inst Global Food Secur, Adv Asset Technol Ctr, Belfast, Antrim, North Ireland

[2] Queens Univ Belfast, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland

[3] Univ Bristol, Inst Clin Neurosci, Sch Clin Sci, Dementia Res Grp, Bristol, Avon, England

[4] Univ Lancaster, Div Biomed & Life Sci, Lancaster, England

[5] Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland

[6] Beaumont Res Inst, Royal Oak, MI USA

来源：

NEUROBIOLOGY OF AGING | 2016年 / 38卷

关键词：

Alzheimer's disease; Metabolites; Metabolomics; Blood; Brain; APP/PS1; APP/PS1 TRANSGENIC MICE; INDEPENDENT PHOSPHOLIPASE A(2); AMYLOID-BETA; MASS-SPECTROMETRY; MOUSE MODEL; THERAPEUTIC IMPLICATIONS; GLUTAMATERGIC SYSTEM; OXIDATIVE STRESS; IN-VIVO; SERUM;

D O I：

10.1016/j.neurobiolaging.2015.11.014

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：151 / 163

页数：13

共 62 条

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[Anonymous], METABOLOMICS

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