TY - JOUR
T1 - Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease
AU - Ahmad, Shahzad
AU - Orellana, Adelina
AU - Kohler, Isabelle
AU - Frölich, Lutz
AU - de Rojas, Itziar
AU - Gil, Silvia
AU - Boada, Mercè
AU - Hernández, Isabel
AU - Hausner, Lucrezia
AU - Bakker, Margot H M
AU - Cabrera-Socorro, Alfredo
AU - Amin, Najaf
AU - Ramírez, Alfredo
AU - Ruiz, Agustín
AU - Hankemeier, Thomas
AU - Van Duijn, Cornelia M
PY - 2020/10/2
Y1 - 2020/10/2
N2 - 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.
AB - 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.
U2 - 10.1186/s13195-020-00680-9
DO - 10.1186/s13195-020-00680-9
M3 - Article
C2 - 33008436
VL - 12
SP - 124
JO - Alzheimer's Research & Therapy
JF - Alzheimer's Research & Therapy
SN - 1758-9193
IS - 1
M1 - 124
ER -