Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed before application to clinical practice.

本研究旨在检测健康受试者以及阿尔茨海默病（Alzheimer’s Disease, AD）患者或患病风险人群血清中游离L-肉碱、乙酰-L-肉碱及34种酰基-L-肉碱的水平。本研究共纳入29例很可能为阿尔茨海默病的患者、18例遗忘型轻度认知障碍（amnestic mild cognitive impairment, aMCI）患者、24例主观性记忆主诉受试者以及46名健康受试者，采用串联质谱法（tandem mass spectrometry）检测肉碱及酰基肉碱的水平。乙酰-L-肉碱的浓度随受试群体依次呈渐进性下降趋势：健康受试者组（均值±标准差，5.6±1.3 μmol/L）→主观性记忆主诉组（4.3±0.9 μmol/L）→轻度认知障碍组（4.0±0.53 μmol/L）→阿尔茨海默病组（3.5±0.6 μmol/L），组间差异具有统计学意义（p<0.001）。具体组间比较差异显著的包括：健康受试者组与主观性记忆主诉组、轻度认知障碍组或阿尔茨海默病组；以及主观性记忆主诉组与阿尔茨海默病组。其余酰基肉碱，如丙二酰基-L-肉碱、3-羟基异戊酰基-L-肉碱、己烯酰基-L-肉碱、癸酰基-L-肉碱、十二酰基-L-肉碱、十二烯酰基-L-肉碱、肉豆蔻酰基-L-肉碱、十四烯酰基-L-肉碱、十六烯酰基-L-肉碱、硬脂酰基-L-肉碱、油酰基-L-肉碱及亚油酰基-L-肉碱，同样呈现出从健康受试者到阿尔茨海默病患病风险人群或患者群体逐步降低的相似趋势。本研究结果提示，血清乙酰-L-肉碱及其他酰基-L-肉碱水平随健康状态向主观性记忆主诉、轻度认知障碍直至阿尔茨海默病患者的连续病程逐渐降低，且部分酰基肉碱的代谢存在紧密关联。此外，血清乙酰-L-肉碱及其他酰基-L-肉碱水平或可用于识别即将表型转化为阿尔茨海默病的患者，以及有望从乙酰-L-肉碱治疗中获益的人群。不过，在应用于临床实践前，仍需通过更大样本量的纵向研究进一步验证上述结论。