Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer’s Disease (AD) Pathology Than in Severe AD Pathology

Metabolites

卷:8

Peter Passmore¹  Bernadette McGuinness¹  Patrick G. Kehoe²  Xiaobei Pan³  Brian D. Green³  Muhammad L. Nasaruddin³  Stewart F. Graham⁴  Christian Hölscher⁵ 

[1] Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast BT12 6BA, Ireland;

[2] Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK;

[3] Institute for Global Food Security (IGFS), Queen’s University Belfast, Stranmillis Road, Belfast BT9 6AG, Ireland;

[4] Metabolomics Research, Beaumont Research Institute 3811 W. 13 Mile Road, Royal Oak, MI 48073, USA;

[5] Research and Experimental Center, Henan University of Traditional Chinese Medicine, Longzihu UniversityCampus, 156 Jinshui Dong Road, Zhengzhou 450000, China;

关键词: fatty acid;    GC-MS;    Alzheimer’s disease;    dementia with Lewy bodies;    metabolomics;    lipidomics;   

DOI  :  10.3390/metabo8040069

来源: DOAJ

【 摘 要 】

Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheimer’s disease (AD), 30 severe AD, and 14 dementia with Lewy bodies (DLB). A total of 24 FA species were identified. Multiple comparison procedures, using stepdown permutation tests, noted higher levels of 13 FAs but the majority of changes were in moderate AD and DLB, rather than severe AD. Subjects with moderate AD and DLB pathology exhibited significantly higher levels of a number of FAs (13 FAs and 12 FAs, respectively). These included nervonic, lignoceric, cis-13,16-docosadienoic, arachidonic, cis-11,14,17-eicosatrienoic, erucic, behenic, α-linolenic, stearic, oleic, cis-10-heptanoic, and palmitic acids. The similarities between moderate AD and DLB were quite striking—arachidic acid was the only FA which was higher in moderate AD than control, and was not similarly affected in DLB. Furthermore, there were no significant differences between moderate AD and DLB. The associations between each FA and a number of variables, including diagnosis, age, gender, Aβ plaque load, tau load, and frontal tissue pH, were also investigated. To conclude, the development of AD or DLB pathology affects brain FA composition but, intriguingly, moderate AD neuropathology impacts this to a much greater extent. Post-mortem delay is a potential confounding factor, but the findings here suggest that there could be a more dynamic metabolic response in the earlier stages of the disease pathology.

【 授权许可】

Unknown