Leukocyte Telomere Length in Alzheimer’s Disease Patients with a Different Rate of Progression

Article type: Research Article

Authors: Tedone, Enzo^a | Arosio, Beatrice^{a; b; *} | Colombo, Federico^c | Ferri, Evelyn^a | Asselineau, Delphine^{d; e; f} | Piette, Francois^g | Gussago, Cristina^a | Belmin, Joel^g | Pariel, Sylvie^g | Benlhassan, Khadija^d | Casati, Martina^a | Bornand, Anne^g | Rossi, Paolo Dionigi^b | Mazzola, Paolo^h | Annoni, Giorgio^h | Doulazmi, Mohamed^{e; f; g} | Mariani, Jean^{e; f; g} | Porretti, Laura^c | Bray, Dorothy H.^d | Mari, Daniela^{a; b}

Affiliations: [a] Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy | [b] Geriatric Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy | [c] Flow Cytometry Service, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy | [d] ImmunoClin Ltd, London, UK | [e] UPMC University Paris 06, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France | [f] CNRS, UMR 8526 Biological Adaptation and Ageing (B2A) Team Brain Development, Repair and Aging (BDRA), Paris, France | [g] AP-HP, DHU FAST GH Pitie-Salpêtrière-Charles Foix, Paris, France. | [h] Geriatric Clinic, Department of Health Science, Milan Center for Neuroscience, University Study of Milano-Bicocca, Milan, Italy

Correspondence: [*] Correspondence to: Beatrice Arosio, PhD, Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy. Tel.: +39 02 55035405; Fax: +39 02 50320735; [email protected]

Abstract: Background: Age and short leukocyte telomeres have been associated with a higher risk of Alzheimer’s disease (AD). Inflammation is involved in AD and it is suggested that anti-inflammatory interleukin-10 (IL-10) may partly antagonize these processes. Objective: The aim is to correlate telomere length (TL) in peripheral blood mononuclear cells (PBMC) from patients with AD to disease progression rate. Moreover, we evaluated whether TL was associated with IL-10 production by unstimulated or amyloid-β (Aβ)-stimulated PBMC. Methods: We enrolled 31 late-onset AD and 20 age-matched healthy elderly (HE). After a two-year follow-up period, patients were retrospectively evaluated as slow-progressing (ADS) (Mini Mental State Examination (MMSE) decline over the two years of follow-up ≤3 points) or fast progressing AD (ADF) (MMSE decline ≥5 points). TL was measured by flow cytometry and in vitro IL-10 production by enzyme-linked immunosorbent assay. Results: TL (mean±SD) for HE, ADS, and ADF was 2.3±0.1, 2.0±0.1, and 2.5±0.1 Kb, respectively. ADS showed a shorter TL compared to HE (p = 0.034) and to ADF (p = 0.005). MMSE decline correlated with TL in AD (R2 = 0.284; p = 0.008). We found a significant difference in IL-10 production between unstimulated and Aβ-stimulated PBMC from ADS (40.7±13.7 versus 59.0±27.0; p = 0.004) but not from ADF (39.7±14.4 versus 42.2±22.4). HE showed a trend toward significance (47.1±25.4 versus 55.3±27.9; p = 0.10). Conclusion: PBMC from ADF may be characterized by an impaired response induced by Aβ and by a reduced proliferative response responsible for the longer telomeres. TL might be a contributing factor in predicting the rate of AD progression.

Keywords: Alzheimer’s disease, disease progression, interleukin-10, peripheral blood mononuclear cells, telomere

DOI: 10.3233/JAD-142808

Journal: Journal of Alzheimer's Disease, vol. 46, no. 3, pp. 761-769, 2015