Circulating Molecular Chaperones in Subjects with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: Data from the Zabut Aging Project

Molecular chaperones play essential roles in many processes such as cell differentiation, tissue homeostasis, and organ remodeling. Recent data indicate that chaperones can act as cytoprotectants for brain cells during the progression of neurodegenerative diseases, including Alzheimer's disease (AD). However, very few data on the levels of chaperones in dementia, including its prodromal phases, have been reported. In this study, we used biological samples and epidemiological data collected during the Zabut Aging Project (a prospective, community-based, cohort study of normal/pathological aging conducted in Sicily, Italy, with a follow-up of ten years) to determine if there is an association between plasma levels of the chaperones Hsp60, Hsp70, and Hsp90 with amnestic mild cognitive impairment (aMCI) and AD. Twenty-six aMCI individuals, 26 AD and 26 controls, matched for age and sex, were enrolled. After adjustment for education, subjects with AD showed significantly higher levels of Hsp60 than aMCI (OR =1.16, 95% CI 1.04-1.30) and controls (OR =1.12, 95% CI 1.03-1.22), while Hsp70 was significantly higher only in AD (OR =1.84, 95% CI 1.09-3.10) than controls. In contrast, circulating levels of Hsp90 were significantly diminished in aMCI (OR = 0.69, 95% CI 0.52-0.91) and AD (OR = 0.51, 95% CI 0.35-0.75) compared to controls. However, these results were no longer significant after adjustment for multiple comparisons. Although the results lost significance after adjustment for multiple comparisons, they are encouraging despite the smallness of the sample and new studies should be carried out with larger populations to determine to what extent sequential measurement of serum chaperones in aMCI and AD can be trusted as indicators of disease status and progression.