Gene promoter methylation and expression of Pin1 differ between patients with frontotemporal dementia and Alzheimer's disease

Evelyn Ferri; Beatrice Arosio; Claudio D'Addario; Daniela Galimberti; Cristina Gussago; Mariangela Pucci; Martina Casati; Chiara Fenoglio; Carlo Abbate; Paolo Dionigi Rossi; Elio Scarpini; Mauro Maccarrone; Daniela Mari

doi:10.1016/j.jns.2016.02.004

Gene promoter methylation and expression of Pin1 differ between patients with frontotemporal dementia and Alzheimer's disease

J Neurol Sci. 2016 Mar 15:362:283-6. doi: 10.1016/j.jns.2016.02.004. Epub 2016 Feb 3.

Authors

Affiliations

¹ Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy; PhD in Nutritional Sciences University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy. Electronic address: evelyn.ferri@unimi.it.
² Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy; Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.
³ Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Piazza Aldo Moro 45, 64100 Teramo, Italy; European Center for Brain Research (CERC)/Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
⁴ Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.
⁵ Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy.
⁶ Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Piazza Aldo Moro 45, 64100 Teramo, Italy.
⁷ Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy; PhD in Nutritional Sciences University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
⁸ Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.
⁹ European Center for Brain Research (CERC)/Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy; Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy.

PMID: 26944164
DOI: 10.1016/j.jns.2016.02.004

Abstract

Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD) share the accumulation of fibrillar aggregates of misfolded proteins. To better understand these neurodegenerative diseases and identify biomarkers in easily accessible cells, we investigated DNA methylation at Pin1 gene promoter and its expression in peripheral blood mononuclear cells of FTD patients. We found a lower gene expression of Pin1 with a higher DNA methylation in three CpG sites at Pin1 gene promoter analysed in FTD subjects, in contrast to a higher gene expression with a lower methylation in AD subjects and controls. These data suggest an important and distinct involvement of Pin1 in these two types of dementia.

Keywords: Alzheimer's disease; Frontotemporal dementia; Methylation; Neurodegeneration; Peripheral marker; Pin1.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnosis
Alzheimer Disease / genetics*
Amyloid beta-Peptides / metabolism
DNA Methylation / genetics*
Female
Frontotemporal Dementia / diagnosis
Frontotemporal Dementia / genetics*
Gene Expression / genetics*
Humans
Male
Mental Status Schedule
Middle Aged
NIMA-Interacting Peptidylprolyl Isomerase / genetics*
NIMA-Interacting Peptidylprolyl Isomerase / metabolism
Promoter Regions, Genetic / genetics*
RNA, Messenger / metabolism
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
NIMA-Interacting Peptidylprolyl Isomerase
RNA, Messenger
tau Proteins
PIN1 protein, human