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Kling, M.A.* ; Goodenowe, D.B.* ; Senanayake, V.* ; MahmoudianDehkordi, S.* ; Arnold, M. ; Massaro, T.J.* ; Baillie, R.* ; Han, X.* ; Leung, Y.Y.* ; Saykin, A.J.* ; Nho, K.* ; Kueider-Paisley, A.* ; Tenenbaum, J.D.* ; Wang, L.S.* ; Shaw, L.M.* ; Trojanowski, J.Q.* ; Kaddurah-Daouk, R.F.*

Circulating ethanolamine plasmalogen indices in Alzheimer's disease: Relation to diagnosis, cognition, and CSF tau.

Alzheimers Dement. 16, 1234-1247 (2020)
Publ. Version/Full Text DOI
Open Access Green: Postprint online available 09/2021
Introduction: Altered lipid metabolism is implicated in Alzheimer's disease (AD), but the mechanisms remain obscure. Aging-related declines in circulating plasmalogens containing omega-3 fatty acids may increase AD risk by reducing plasmalogen availability.Methods: We measured four ethanolamine plasmalogens (PlsEtns) and four closely related phosphatidylethanolamines (PtdEtns) from the Alzheimer's Disease Neu-roimaging Initiative (ADNI; n = 1547 serum) and University of Pennsylvania (U Penn; n = 112 plasma) cohorts, and derived indices reflecting PlsEtn and PtdEtn metabolism: PL-PX (PlsEtns), PL/PE (PlsEtn/PtdEtn ratios), and PBV (plasmalogen biosynthesis value; a composite index). We tested associations with baseline diagnosis, cognition, and cere-brospinal fluid (CSF) AD biomarkers.Results: Results revealed statistically significant negative relationships in ADNI between AD versus CN with PL-PX (P = 0.007) and PBV (P = 0.005), late mild cognitive impairment (LMCI) versus cognitively normal (CN) with PL-PX (P = 2.89 x 10(-5)) and PBV (P = 1.99 x 10(-4), and AD versus LMCI with POPE (P = 1.85 x 10(-4)). In the UPenn cohort, AD versus CN diagnosis associated negatively with PL/PE (P = 0.0191) and PBV (P = 0.0296).In ADNI, cognition was negatively associated with plasmalogen indices, including Alzheimer's Disease Assessment Scale 13-item cognitive subscale (ADAS-Cog13; PL-PX: P = 3.24 x 10(-6); PBV: P = 6.92 x 10(-5)) and Mini-Mental State Examination (MMSE; PL-PX: P = 1.28 x 10(-9); PBV: P = 6.50 x 10(-9)). In the UPenn cohort, there was a trend toward a similar relationship of MMSE with PL/PE (P = 0.0949).In ADN I, CSF total-tau was negatively associated with PL-PX (P = 5.55 x 10(-6)) and PBV (P = 7.77 x 10(-6)). Additionally, CSF t-tau/A beta(1-42) 42 ratio was negatively associated with these same indices (PL-PX, P= 2.73 x 10(-6); PBV, P = 4.39 x 10(-6)). In the UPenn cohort, PL/PE was negatively associated with CSF total-tau (P = 0.031) and t-tau/A beta(1-42) (P = 0.021). CSF A beta(1-42) was not significantly associated with any of these indices in either cohort.Discussion: These data extend previous studies by showing an association of decreased plasmalogen indices with AD, mild cognitive impairment (MCI), cognition, and CSF tau. Future studies are needed to better define mechanistic relationships, and to test the effects of interventions designed to replete serum plasmalogens.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Case-control Study ; Dementia ; Lipidomics ; Mass Spectrometry ; Metabolomics ; Mild Cognitive Impairment ; Phosphatidylethanolamines ; Plasmenylethanolamines; Docosahexaenoic Acid; Deficiency; Plasmenylethanolamine; Dementia; Health; Brain; Lipoprotein; Metabolism; Decrease; Fusion
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Quellenangaben Volume: 16, Issue: 9, Pages: 1234-1247 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY [u.a.]
Reviewing status
Grants Eisai Inc.
Elan Pharmaceuticals, Inc.
Eli Lilly and Company
EuroImmun
F. Hoffmann-La Roche Ltd
Genentech, Inc.
Fujirebio
GE Healthcare
IXICO Ltd.
Janssen Alzheimer Immunotherapy Research & Development, LLC
CereSpir, Inc.
Bristol-Myers Squibb Company
Biogen
National Institute on Aging grant
Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health)
DOD ADNI (Department of Defense award)
National Institute on Aging
AbbVie
Alzheimer's Association
Alzheimer's Drug Discovery Foundation
Araclon Biotech
BioClinica, Inc.
Johnson & Johnson Pharmaceutical Research & Development LLC
Lumosity
National Library of Medicine
National Library of Medicine
National Institute of Biomedical Imaging and Bioengineering
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NIA
Canadian Institutes of Health Research
Transition Therapeutics
Lundbeck
Merck Co., Inc.
Meso Scale Diagnostics, LLC
NeuroRx Research
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Novartis Pharmaceuticals Corporation
Pfizer Inc.
Piramal Imaging
Servier
Takeda Pharmaceutical Company
Indiana University-IU Health Strategic Neuroscience Research Initiative