Lysosomal β-Galactosidase and β-Hexosaminidase Activities Correlate with Clinical Stages of Dementia Associated with Alzheimer's Disease and Type 2 Diabetes Mellitus

Article type: Research Article

Authors: Tiribuzi, Roberto^a | Orlacchio, Antonio^{b; c} | Crispoltoni, Lucia^a | Maiotti, Mariangela^d | Zampolini, Mauro^d | De Angeliz, Massimiliano^e | Mecocci, Patrizia^f | Cecchetti, Roberta^f | Bernardi, Giorgio^{b; c} | Datti, Alessandro^a | Martino, Sabata^a | Orlacchio, Aldo^{a; *}

Affiliations: [a] Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Sezione di Biochimica e Biologia Molecolare, University of Perugia, Perugia, Italy | [b] Laboratorio di Neurogenetica, CERC-IRCCS Santa Lucia, Rome, Italy | [c] Dipartimento di Neuroscienze, University “Tor Vergata”, Rome, Italy | [d] Neuropsicologia Clinica, Ospedale S. Giovanni Battista, Foligno, Italy | [e] U.O. S.S. Ambulatoriale di Diabetologia Di.M.I., University of Perugia, Perugia, Italy | [f] Sezione di Gerontologia e Geriatria, Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy

Correspondence: [*] Correspondence to: Prof. Aldo Orlacchio, Ph.D., Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Sezione di Biochimica e Biologia Molecolare, University of Perugia, via del Giochetto, 06126 Perugia, Italy. Tel./Fax: +39 0755852187. E-mail: orly@unipg.it.

Abstract: Multiple epidemiological studies have shown that individuals affected by type-2 diabetes mellitus (T2DM) carry a 2-to-5-fold higher risk of developing Alzheimer's disease (AD) when compared to non-diabetic subjects. Thus, biochemical parameters that can be easily and routinely assessed for high-confidence evaluation of diabetic conditions leading to AD (AD-T2DM) are regarded as efficient tools aimed at early diagnosis and, in turn, timely AD treatment. In this regard, the activity of lysosomal glycohydrolases may of use, in light of the implication of these enzymes in early events that underlie AD pathology and an overt correlation, in diabetes, between altered metabolic homeostasis, abnormal glycohydrolase secretion in body fluids, and occurrence of diabetic complications. Based on marked up-regulation previously shown in a peripheral, cell-based model of AD, we selected β-Galactosidase, β-Hexosaminidase, and α-Mannosidase to discriminate T2DM from AD-T2DM subjects. A screen of 109, 114, and 116 patients with T2DM, AD and AD-T2DM, respectively, was performed by testing enzyme activities in both blood plasma and peripheral blood mononuclear cells. Compared to age-matched, healthy controls (n = 122), β-Galactosidase and β-Hexosaminidase activities markedly diverged across the three groups, whereas virtually unchanged values were observed for α-Mannosidase. In particular, plasma β-Galactosidase and β-Hexosaminidase levels were higher in patients with AD-T2DM compared to those with T2DM, suggesting different mechanisms leading to enzyme secretion. Statistical analyses based on ROC curves showed that both β-Galactosidase and β-Hexosaminidase activities, either intracellular or plasma-secreted, may be used to discriminate AD patients from controls and AD-T2DM from T2DM patients.

Keywords: Alzheimer's disease, diagnostic correlation, lysosomal glycohydrolases, type 2 diabetes

DOI: 10.3233/JAD-2011-100525

Journal: Journal of Alzheimer's Disease, vol. 24, no. 4, pp. 785-797, 2011