Corso Gaetano, Cristofano Adriana, Sapere Nadia, la Marca Giancarlo, Angiolillo Antonella, Vitale Michela, Fratangelo Roberto, Lombardi Teresa, Porcile Carola, Intrieri Mariano, Di Costanzo Alfonso
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Centre for Research and Training in Medicine for Aging, Department of Medicine and Health Sciences "Vincenzo Tiberio," University of Molise, Campobasso, Italy.
Dement Geriatr Cogn Dis Extra. 2017 May 4;7(1):143-159. doi: 10.1159/000466688. eCollection 2017 Jan-Apr.
BACKGROUND/AIMS: Abnormalities in the plasma amino acid profile have been reported in Alzheimer disease (AD), but no data exist for the prodromal phase characterized by subjective memory complaint (SMC). It was our aim to understand if serum amino acid levels change along the continuum from normal to AD, and to identify possible diagnostic biomarkers.
Serum levels of 15 amino acids and 2 organic acids were determined in 4 groups of participants - 29 with probable AD, 18 with mild cognitive impairment (MCI), 24 with SMC, and 46 cognitively healthy subjects (HS) - by electrospray tandem mass spectrometry.
Glutamate, aspartate, and phenylalanine progressively decreased, while citrulline, argi-ninosuccinate, and homocitrulline progressively increased, from HS over SMC and MCI to AD. The panel including these 6 amino acids and 4 ratios (glutamate/citrulline, citrulline/phenylalanine, leucine plus isoleucine/phenylalanine, and arginine/phenylalanine) discriminated AD from HS with about 96% accuracy. Other panels including 20 biomarkers discriminated SMC or MCI from AD or HS with an accuracy ranging from 88 to 75%.
Amino acids contribute to a characteristic metabotype during the progression of AD along the continuum from health to frank dementia, and their monitoring in elderly individuals might help to detect at-risk subjects.
背景/目的：已有报道称阿尔茨海默病（AD）患者血浆氨基酸谱存在异常，但对于以主观记忆主诉（SMC）为特征的前驱期尚无相关数据。我们的目的是了解血清氨基酸水平在从正常到AD的连续过程中是否发生变化，并确定可能的诊断生物标志物。
通过电喷雾串联质谱法测定了4组参与者（29例可能患有AD、18例轻度认知障碍（MCI）、24例有SMC和46例认知健康受试者（HS））血清中15种氨基酸和2种有机酸的水平。
从HS到SMC、MCI再到AD，谷氨酸、天冬氨酸和苯丙氨酸逐渐降低，而瓜氨酸、精氨琥珀酸和高瓜氨酸逐渐升高。包含这6种氨基酸和4种比率（谷氨酸/瓜氨酸、瓜氨酸/苯丙氨酸、亮氨酸加异亮氨酸/苯丙氨酸和精氨酸/苯丙氨酸）的检测组区分AD和HS的准确率约为96%。其他包含20种生物标志物的检测组区分SMC或MCI与AD或HS的准确率在88%至75%之间。
在AD从健康到明显痴呆的连续进展过程中，氨基酸有助于形成特征性代谢型，对老年人进行氨基酸监测可能有助于检测高危人群。
