title: DNA methylation in the apolipoprotein-A1 gene is associated with episodic memory performance in healthy older individuals.
abstract: BACKGROUND
  DNA methylation variation has been implicated in memory, cognitive performance, and dementia. Plasma apolipoprotein-A1 (ApoA1) levels may act as a biomarker of age-associated cognitive performance and decline.
  
  
  OBJECTIVE
  To estimate the heritability of plasma ApoA1 protein levels; to examine DNA methylation variation within the APOA1 gene; and to investigate whether APOA1 methylation is associated with plasma ApoA1 levels and episodic memory performance.
  
  
  METHODS
  Heritability of ApoA1 protein levels in Older Australian Twins Study (OATS) was assessed using structural equation modelling. APOA1 methylation levels were assayed in two cohorts of cognitively normal older individuals. The methylation status of 12 CpGs in 24 twin pairs from OATS was assayed using the Illumina 450K methylation array. Candidate CpGs were assayed in 454 individuals from Sydney Memory and Ageing Study (Sydney MAS) using pyrosequencing. Regression analyses assessed associations between APOA1 methylation levels, ApoA1 plasma levels, and memory performance.
  
  
  RESULTS
  No significant heritability was observed for ApoA1 protein levels. APOA1 candidate-gene analyses revealed CpG sites associated with memory performance in the twin study (p < 0.050). Replication of an association between methylation of a specific CpG (cg03010018) in APOA1 and memory performance was observed in Sydney MAS (β = -0.145, p = 0.010). Methylation of this CpG site was also significantly correlated with ApoA1 protein levels (β = 0.161, p = 0.019). However, no relationship between a composite memory domain score and methylation was observed (p = 0.389).
  
  
  CONCLUSIONS
  Findings demonstrated that epigenetic control of APOA1 expression and DNA methylation levels are associated with episodic memory performance in older adults.
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lazarus
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lee
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kochan
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Dementia Collaborative Research Centre - Assessment and Better Care, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Department of Psychiatry, University of Melbourne, Australia National Ageing Research Institute, Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Centre for Healthy Brain Aging, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia Neuropsychiatric Institute (NPI), Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.affiliation: Neuroscience Research Australia, Sydney, NSW, Australia School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D001315:Australia; D003071:Cognition / Q000502:physiology; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D009483:Neuropsychological Tests; D012044:Regression Analysis; D014430:Twins, Monozygotic
chemical_list: D016632:Apolipoprotein A-I
keywords: Aging; DNA methylation; apolipoprotein A1; epigenomics; episodic memory