Journal
METABOLITES
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/metabo10110438
Keywords
Alzheimer's disease; post-mortem delay; human brain metabolomics; rat brain metabolomics; mass spectrometry; brain tissue quality
Categories
Funding
- Endocore Research Associates, New Zealand [60147]
- Maurice and Phyllis Paykel Trust, New Zealand [3627036]
- Lottery Health New Zealand [3626585, 3702766]
- Maurice Wilkins Centre for Molecular Biodiscovery, New Zealand [Tertiary Education Commission] [9341-3622506]
- Lee Trust, New Zealand
- University of Auckland [JXU058]
- Oakley Mental Health Research Foundation [3456030, 3627092, 3701339, 3703253, 3702870]
- Ministry of Business, Innovation & Employment, New Zealand [UOAX0815]
- Neurological Foundation of New Zealand
- Medical Research Council [UK] [MR/L010445/1, MR/L011093/1]
- Alzheimer's research UK [ARUK-PPG2014B-7]
- University of Manchester
- Northwest Regional Development Agency
- MFT
- New Zealand Ministry of Business, Innovation & Employment (MBIE) [UOAX0815] Funding Source: New Zealand Ministry of Business, Innovation & Employment (MBIE)
- MRC [MR/L023784/2, MR/L023784/1, G1100540, G0400074, G0502157, G0900652] Funding Source: UKRI
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The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer's disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables. Cingulate gyrus was obtained from AD cases and controls, from three brain banks. Gas chromatography-mass spectrometry (GC-MS) was used to measure and compare the levels of 66 identifiable metabolites in these tissues to determine effects of tissue-collection variables. The effect of PMD was further investigated by analysis of rat brain cortex and cerebellum collected following post-mortem delays (PMDs) of zero to 72 h. Metabolite levels between cases and controls were not replicable across cohorts with variable age- and gender-matching, PMD, and control Braak staging. Analysis of rat tissues found significant effects of PMD on 31 of 63 identified metabolites over periods up to 72 h. PMD must be kept under 24 h for metabolomics analyses on brain tissues to yield replicable results. Tissues should also be well age- and gender-matched, and Braak stage in controls should be kept to a minimum in order to minimize the impact of these variables in influencing metabolite variability.
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