Abstract | BACKGROUND: 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.
|
Authors | Shahzad Ahmad, Adelina Orellana, Isabelle Kohler, Lutz Frölich, Itziar de Rojas, Silvia Gil, Mercè Boada, Isabel Hernández, Lucrezia Hausner, Margot H M Bakker, Alfredo Cabrera-Socorro, Najaf Amin, Alfredo Ramírez, Agustín Ruiz, Thomas Hankemeier, Cornelia M Van Duijn |
Journal | Alzheimer's research & therapy
(Alzheimers Res Ther)
Vol. 12
Issue 1
Pg. 124
(10 02 2020)
ISSN: 1758-9193 [Electronic] England |
PMID | 33008436
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Amyloid beta-Peptides
- Biomarkers
- Lysophospholipids
- Peptide Fragments
- tau Proteins
|
Topics |
- Alzheimer Disease
(genetics)
- Amyloid beta-Peptides
- Biomarkers
- Cognitive Dysfunction
(genetics)
- Cohort Studies
- Disease Progression
- Humans
- Lysophospholipids
- Peptide Fragments
- tau Proteins
|