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P1‐298: CEREBROSPINAL FLUID AND PLASMA LEVELS OF LYSOPHOSPHATIDIC ACIDS (LPAS) ASSOCIATE WITH CEREBROSPINAL FLUID Aβ‐42 AND P‐TAU
Author(s) -
Ahmad Shahzad,
Kohler Isabelle,
Orellana Adelina,
Frölich Lutz,
Rojas Itziar,
Gil Silvia,
Hernandez Isabel,
Hausner Lucrezia,
Kawalia Amit,
Bakker Margot H.M.,
Socorro Alfredo Cabrera,
Amin Najaf,
Ramirez Alfredo,
Ruiz Agustin,
Hankemeier Thomas,
Duijn Cornelia M.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.304
Subject(s) - cerebrospinal fluid , medicine , apolipoprotein e , metabolite , oncology , endocrinology , disease
of global and medial temporal lobe atrophy (GCA scale 0-3, MTAscale: 0-4) and white matter hyperintensities (WMH; Fazekas scale; 0-3) with 3 linear regression models; an unadjusted model (model 1), a model including adjustment for sex and age (model 2), and a model including additional adjustment for cardiovascular disease and lipid lowering medication (model 3). The results listed in Table 1 and 2 pass a Bonferroni corrected threshold for significance (p1⁄40.05/1091⁄44.6x10). Results: Thirty-one metabolites were associated with GCA score (Table 1). Lower concentrations of VLDL and triglycerides and higher concentrations of HDL were associated with more atrophy (higher GCA scores). Lower levels of 6 metabolites, including linoleic acid, omega-6 fatty acids and VLDL cholesterol were associated with more WMH (Table 2). Higher levels of citrate and lower levels of histidine were associated with more GCA andMTA (B6SE 0.1160.02, 0.1260.03 for citrate, -0.0960.02, -0.1060.03 for histidine (Figure 1)). The association between lower triglycerides and VLDL levels and higher GCA scores did not alter after correction for clinical variables in Model 2 and 3. Conclusions:Multiple metabolites associate with the extent of neurodegenerative MRI measures. Cholesterol metabolism is important for many processes such as cell membrane structure and synaptic integrity. Previous studies report lower levels of total cholesterol in AD and elevated citrate levels and decreased VLDL particle size predictive for all-causemortality. Perhaps the metabolic changes shown here are systemic markers of frailty in AD.