Lysosomal β-galactosidase and β-hexosaminidase activities correlate with clinical stages of dementia associated with Alzheimer's disease and type 2 diabetes mellitus

Aldo Orlacchio, Roberto Tiribuzi, Antonio Orlacchio, Lucia Crispoltoni, Mariangela Maiotti, Mauro Zampolini, Massimiliano De Angeliz, Patrizia Mecocci, Roberta Cecchetti, Giorgio Bernardi, Alessandro Datti, Sabata Martino

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)785-797
Number of pages13
JournalJournal of Alzheimer's Disease
Volume24
Issue number4
DOIs
Publication statusPublished - 2011

Keywords

  • Alzheimer's disease
  • diagnostic correlation
  • lysosomal glycohydrolases
  • type 2 diabetes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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  • Cite this

    Orlacchio, A., Tiribuzi, R., Orlacchio, A., Crispoltoni, L., Maiotti, M., Zampolini, M., De Angeliz, M., Mecocci, P., Cecchetti, R., Bernardi, G., Datti, A., & Martino, S. (2011). Lysosomal β-galactosidase and β-hexosaminidase activities correlate with clinical stages of dementia associated with Alzheimer's disease and type 2 diabetes mellitus. Journal of Alzheimer's Disease, 24(4), 785-797. https://doi.org/10.3233/JAD-2011-100525