Nasaruddin Muhammad Luqman, Hölscher Christian, Kehoe Patrick, Graham Stewart Francis, Green Brian Desmond
Institute for Global Food Security (IGFS), Queen's University Belfast Stranmillis Road, Belfast Northern Ireland, BT9 6AG, UK.
Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University Lancaster LA1 4YQ, UK.
Am J Transl Res. 2016 Jan 15;8(1):154-65. eCollection 2016.
Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia.
脂质代谢紊乱是人类阿尔茨海默病（AD）公认的一个特征。本研究采用气相色谱 - 质谱联用（GC - MS）分析法对脂肪酸甲酯（FAMEs）进行分析，以描绘死后新皮质组织（布罗德曼7区）中所有可检测到的脂肪酸（FA）种类。对29名受试者（n = 15名年龄匹配的对照者；n = 14名晚期AD患者）进行了定量靶向分析。FAMEs的GC - MS分析共检测到24种FA，其中20种可进行完全定量。结果显示AD脑内FA浓度显著且广泛升高。AD中有9种FA升高，其中顺式 - 13,16 - 二十二碳烯酸升高最多（170%；P = 0.033）。有趣的是，二十二碳六烯酸（DHA；C22:6）浓度升高（47%；P = 0.018），这与其他研究在AD发病后某些脑区的发现（未改变或降低）相矛盾。此外，我们的结果似乎表明受试者性别会影响AD患者脑内FA水平（但不影响年龄匹配的对照者）。在AD患者中，7种FA在男性中的含量显著高于女性。这些初步发现指出FA紊乱在AD病理学中可能具有重要意义。需要进一步的研究来确定这些变化是否受疾病严重程度或不同类型痴呆的影响。
