Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease

被引：15

作者：

Ahmad, Shahzad ^{[1
]}

Orellana, Adelina ^{[2
,3
,4
]}

Kohler, Isabelle ^{[5
]}

Froelich, Lutz ^{[6
]}

de Rojas, Itziar ^{[2
,3
,4
]}

Gil, Silvia ^{[2
,3
,4
]}

Boada, Merce ^{[2
,3
,4
]}

Hernandez, Isabel ^{[2
,3
,4
]}

Hausner, Lucrezia ^{[6
,7
]}

Bakker, Margot H. M. ^{[8
]}

Cabrera-Socorro, Alfredo ^{[9
]}

Amin, Najaf ^{[1
]}

Ramirez, Alfredo ^{[10
,11
]}

Ruiz, Agustin ^{[2
,3
,4
]}

Hankemeier, Thomas ^{[1
,5
]}

Van Duijn, Cornelia M. ^{[1
,12
]}

机构：

[1] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[2] Aplicades Univ Int Catalunya, Inst Catala Neurociencies, Res Ctr, Barcelona, Spain

[3] Aplicades Univ Int Catalunya, Inst Catala Neurociencies, Memory Clin Fundacio ACE, Barcelona, Spain

[4] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

[5] Leiden Univ, Leiden Acad Ctr Drug Res, Div Syst Biomed & Pharmacol, Leiden, Netherlands

[6] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Geriatr Psychiat, D-68159 Mannheim, Germany

[7] Heidelberg Univ, Med Fac Mannheim, Inst Cognit & Clin Neurosci, Cent Inst Mental Hlth, D-68159 Mannheim, Germany

[8] AbbVie Deutschland GmbH & Co KG, Discovery Res, Knollstr, D-67061 Ludwigshafen, Germany

[9] Janssen Pharmaceut NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

[10] Univ Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany

[11] Univ Cologne, Med Fac, Dept Psychiat & Psychotherapy, Div Neurogenet & Mol Psychiat, Cologne, Germany

[12] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

来源：

ALZHEIMERS RESEARCH & THERAPY | 2020年 / 12卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

Lysophosphatidic acids; Pro-inflammatory phospholipids; Signaling lipids; CSF biomarkers; Alzheimer's disease; MCI; MILD COGNITIVE IMPAIRMENT; TRAUMATIC BRAIN-INJURY; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; VASCULAR DEMENTIA; MOLECULAR-CLONING; LIPID MEDIATORS; LPA RECEPTORS; TAU; BETA-AMYLOID(1-42);

D O I：

10.1186/s13195-020-00680-9

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer's disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD. Methods The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, A beta-42,p-tau, and total tau levels overall and stratified byAPOEgenotype and with MCI to AD progression. Results Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, A beta-42,p-tau, and total tau, while LPA C14:0 and C20:1 associated only with A beta-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with A beta-42 levels was found only in APOE epsilon 4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort. Conclusions Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.

引用

页数：13

共 60 条

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