DNA Hypomethylation in Blood Links B3GALT4 and ZADH2 to Alzheimer's Disease

J Alzheimers Dis. 2018;66(3):927-934. doi: 10.3233/JAD-180592.

Abstract

Differentially methylated positions (DMPs) between persons with and without late-onset Alzheimer's disease (LOAD) were observed at 477 of 769,190 loci in a plurality of genes. Of these, 17 were shared with DMPs identified using clinical LOAD markers analyzed independently as continuous variables comprising Rey Auditory Verbal Learning Test scores, cerebrospinal fluid total tau (t-tau) and phosphorylated tau 181 (p-tau181) levels, and t-tau/Aβ1-42 (Aβ42), p-tau181/Aβ42, and Aβ42/Aβ1-40 (Aβ40) ratios. In patients with LOAD, 12 of the shared 17 DMPs were hypomethylated in B3GALT4 (Beta-1,3-galatcosyltransferase 4) (EC 2.4.1.62), and 5 were hypomethylated in ZADH2 (Prostaglandin reductase 3) (EC 1.3.1.48).

Keywords: Amyloid; DNA methylation; late-onset Alzheimer’s disease; tau proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Antigens, Surface / genetics*
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / genetics
  • DNA Methylation*
  • Galactosyltransferases / genetics*
  • Humans
  • Memory and Learning Tests
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Trail Making Test
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Antigens, Surface
  • Peptide Fragments
  • ZADH2 protein, human
  • tau Proteins
  • Galactosyltransferases
  • UDP-Gal-betaGlcNAc beta 1,3-galactosyltransferase, human