Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology

Alzheimer's Disease Neuroimaging Initiative, Alzheimer Disease Metabolomics Consortium

Research output: Contribution to journalArticle

Abstract

Introduction: Comorbidity with metabolic diseases indicates that lipid metabolism plays a role in the etiology of Alzheimer's disease (AD). Comprehensive lipidomic analysis can provide new insights into the altered lipid metabolism in AD. Method: In this study, a total 349 serum lipids were measured in 806 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative Phase 1 cohort and analyzed using lipid-set enrichment statistics, a data mining method to find coregulated lipid sets. Results: We found that sets of blood lipids were associated with current AD biomarkers and with AD clinical symptoms. AD diagnosis was associated with 7 of 28 lipid sets of which four also correlated with cognitive decline, including polyunsaturated fatty acids. Cerebrospinal fluid amyloid beta (Aβ1-42) correlated with glucosylceramides, lysophosphatidylcholines and unsaturated triacylglycerides; cerebrospinal fluid total tau and brain atrophy correlated with monounsaturated sphingomyelins and ceramides, in addition to EPA-containing lipids. Discussion: AD-associated lipid sets indicated that lipid desaturation, elongation, and acyl chain remodeling processes are disturbed in AD subjects. Monounsaturated lipid metabolism was important in early stages of AD, whereas the polyunsaturated lipid metabolism was associated with later stages of AD. Our study provides several new hypotheses for studying the role of lipid metabolism in AD.

Original languageEnglish (US)
Pages (from-to)619-627
Number of pages9
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume11
DOIs
StatePublished - Dec 1 2019

Fingerprint

Alzheimer Disease
Lipids
Serum
Lipid Metabolism
Cerebrospinal Fluid
Glucosylceramides
Lysophosphatidylcholines
Data Mining
Sphingomyelins
Ceramides
Metabolic Diseases
Unsaturated Fatty Acids
Amyloid
Neuroimaging
Atrophy
Comorbidity
Biomarkers
Brain

Keywords

  • Alzheimer's disease
  • Dyslipidemias
  • Lipid biochemistry
  • Lipidomics
  • Mass spectrometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology. / Alzheimer's Disease Neuroimaging Initiative; Alzheimer Disease Metabolomics Consortium.

In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Vol. 11, 01.12.2019, p. 619-627.

Research output: Contribution to journalArticle

Alzheimer's Disease Neuroimaging Initiative ; Alzheimer Disease Metabolomics Consortium. / Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology. In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. 2019 ; Vol. 11. pp. 619-627.
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