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

Autor: Mercè Boada, Alfredo Ramirez, Itziar de Rojas, Isabel Hernández, Silvia Gil, Alfredo Cabrera-Socorro, Isabelle Kohler, Agustín Ruiz, Thomas Hankemeier, Cornelia M. van Duijn, Najaf Amin, Margot H.M. Bakker, Lutz Frölich, Adelina Orellana, Lucrezia Hausner, Shahzad Ahmad
Přispěvatelé: Epidemiology, AIMMS, BioAnalytical Chemistry
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Apolipoprotein E
medicine.medical_specialty
Neurology
Cognitive Neuroscience
tau Proteins
Disease
lcsh:RC346-429
lcsh:RC321-571
Pathogenesis
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Cerebrospinal fluid
SDG 3 - Good Health and Well-being
Alzheimer Disease
Internal medicine
Genotype
medicine
Dementia
Humans
Cognitive Dysfunction
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
CSF biomarkers
lcsh:Neurology. Diseases of the nervous system
Amyloid beta-Peptides
business.industry
Research
Lysophosphatidic acids
Neurodegeneration
Pro-inflammatory phospholipids
medicine.disease
Peptide Fragments
MCI
3. Good health
030104 developmental biology
Signaling lipids
Disease Progression
lipids (amino acids
peptides
and proteins)
Neurology (clinical)
Lysophospholipids
business
Alzheimer’s disease
030217 neurology & neurosurgery
Biomarkers
Zdroj: Alzheimer's Research & Therapy
Alzheimers Research & Therapy, 12(1):124. BioMed Central Ltd.
Alzheimer's Research & Therapy, 12(1):124. BioMed Central
Alzheimer’s Research & Therapy, Vol 12, Iss 1, Pp 1-13 (2020)
Alzheimer’s Research & Therapy, 12, 124. BMC
Ahmad, S, Orellana, A, Kohler, I, Frölich, L, de Rojas, I, Gil, S, Boada, M, Hernández, I, Hausner, L, Bakker, M H M, Cabrera-Socorro, A, Amin, N, Ramírez, A, Ruiz, A, Hankemeier, T & Van Duijn, C M 2020, ' Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease ', Alzheimer's Research & Therapy, vol. 12, no. 1, 124, pp. 124 . https://doi.org/10.1186/s13195-020-00680-9
ISSN: 1758-9193
DOI: 10.1186/s13195-020-00680-9
Popis: 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.
Databáze: OpenAIRE
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