title: Altered proteolysis in fibroblasts of Alzheimer patients with predictive implications for subjects at risk of disease.
abstract: There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer's disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOE ε 4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a useful in vitro model for further studies on the pathogenetic process of AD.
authors.affiliation: Section of Experimental Pathology and Oncology, Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Alessandra
authors.identifier: 0000-0002-5673-1780
authors.initials: A
authors.lastname: Mocali
authors.affiliation: Section of Experimental Pathology and Oncology, Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Della Malva
authors.affiliation: Department of Internal Medicine, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Abete
authors.affiliation: Geriatric Unit of ASL 4, Prato Hospital, 59100 Prato, Italy.
authors.forename: Vito Antonio
authors.initials: VA
authors.lastname: Mitidieri Costanza
authors.affiliation: Geriatric Unit of ASL 4, Prato Hospital, 59100 Prato, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bavazzano
authors.affiliation: Department of Public Health, University of Florence, 50134 Florence, Italy.
authors.forename: Vieri
authors.initials: V
authors.lastname: Boddi
authors.affiliation: 1st Unit of General Surgery and Transplantation, Careggi Hospital, 50134 Florence, Italy.
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez
authors.affiliation: Department of Internal Medicine, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dessì
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pani
authors.affiliation: Section of Experimental Pathology and Oncology, Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Paoletti