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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<jats:italic>\u03b5<\/jats:italic>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<jats:italic>in vitro<\/jats:italic>model for further studies on the pathogenetic process of AD.<\/jats:p>","DOI":"10.1155\/2014\/520152","type":"journal-article","created":{"date-parts":[[2014,5,18]],"date-time":"2014-05-18T21:05:27Z","timestamp":1400447127000},"page":"1-8","source":"Crossref","is-referenced-by-count":11,"title":["Altered Proteolysis in Fibroblasts of Alzheimer Patients with Predictive Implications for Subjects at Risk of Disease"],"prefix":"10.1155","volume":"2014","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-1780","authenticated-orcid":true,"given":"Alessandra","family":"Mocali","sequence":"first","affiliation":[{"name":"Section of Experimental Pathology and Oncology, Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzia","family":"Della 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