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

Alzheimer’s Research & Therapy

Alfredo Ramírez¹  Cornelia M. Van Duijn²  Shahzad Ahmad²  Najaf Amin²  Thomas Hankemeier²  Lucrezia Hausner³  Lutz Frölich³  Margot H. M. Bakker⁴  Isabelle Kohler⁵  Alfredo Cabrera-Socorro⁶  Isabel Hernández⁷  Mercè Boada⁷  Itziar de Rojas⁷  Silvia Gil⁷  Adelina Orellana⁷  Agustín Ruiz⁷ 

[1] Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn;Department of Epidemiology, Erasmus Medical Centre;Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg;Discovery Research, AbbVie Deutschland GmbH & Co. KG;Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University;Janssen Pharmaceutical NV;Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències, Aplicades. Universitat Internacional de Catalunya;

关键词: Lysophosphatidic acids;    Pro-inflammatory phospholipids;    Signaling lipids;    CSF biomarkers;    Alzheimer’s disease;    MCI;   

DOI  :  10.1186/s13195-020-00680-9

来源: DOAJ

【 摘 要 】

Abstract 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, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype 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, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-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 Aβ-42 levels was found only in APOE ε4 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.

【 授权许可】

Unknown