PICALM Gene Methylation in Blood of Alzheimer’s Disease Patients Is Associated with Cognitive Decline

Article type: Research Article

Authors: Mercorio, Roberta^{a; 1} | Pergoli, Laura^{a; 1} | Galimberti, Daniela^b | Favero, Chiara^a | Carugno, Michele^a | Dalla Valle, Elisabetta^b | Barretta, Francesco^a | Cortini, Francesca^a | Scarpini, Elio^b | Valentina, Valentina Bollati^a | Pesatori, Angela Cecilia^{a; c; *}

Affiliations: [a] EPIGET - Epidemiology, Epigenetics and Toxicology Lab - Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy | [b] Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [c] Epidemiology Unit, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

Correspondence: [*] Correspondence to: Angela Cecilia Pesatori, EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via San Barnaba 8, Milan, Italy. Tel.: +39 02 50320120; E-mail: angela.pesatori@unimi.it.

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

Abstract: Epigenetic mechanisms might be involved in Alzheimer’s disease (AD). Genetic polymorphisms in several genes, including APOE (Apolipoprotein E), PSEN1 (Presenilin 1), CR1 (Complement receptor 1), and PICALM (Phosphatidylinositol binding clathrin assembly protein), have been associated to an increased AD risk. However, data regarding methylation of these specific genes are lacking. We evaluated DNA methylation measured by quantitative bisulfite-PCR pyrosequencing in 43 AD patients and 38 healthy subjects (HS). In a multivariate age- and gender-adjusted model, PICALM methylation was decreased in AD compared to HS (mean = 3.54 and 4.63, respectively, p = 0.007). In AD, PICALM methylation level was also positively associated to Mini-Mental Scale Examination (MMSE) score (percent change 3.48%, p = 0.008). Moreover, a negative association between PICALM methylation and age was observed only in HS (percent change – 2.29%, p = 0.002). In conclusion, our data suggest a possible role of PICALM methylation in AD, particularly related to cognitive function. Given the small study sample and the associative nature of our study, further prospective investigations are required to assess the dynamics of DNA methylation in the early stages of AD development.

Keywords: Alzheimer’s disease, epigenetics, methylation, Mini-Mental State Examination, PICALM

DOI: 10.3233/JAD-180242

Journal: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 283-292, 2018