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

Article type: Short Communication

Authors: Madrid, Andy^{a; b} | Hogan, Kirk J.^{c; d; *; 1} | Papale, Ligia A.^a | Clark, Lindsay R.^{d; e; f} | Asthana, Sanjay^{e; f} | Johnson, Sterling C.^{d; e; f} | Alisch, Reid S.^{a; 1}

Affiliations: [a] Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [b] Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [c] Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [d] Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [e] Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [f] Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

Correspondence: [*] Correspondence to: Kirk J. Hogan, Department of Anesthesiology, Wisconsin Alzheimer’s Institute, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA. Tel.: +1 608 263 8100; E-mail: WEML [email protected].

Note: [1] These authors contributed equally to this work.

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

DOI: 10.3233/JAD-180592

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 927-934, 2018