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Plasma levels of amyloid ß-protein 42 are increased in women with mild cognitive impairment

From the Departments of Neurosciences (Drs. Assini, Vitali, Colucci, Giliberto, Borghi, Piccini, and Tabaton, and M.L. Inglese and S. Volpe) and Internal Medicine (Dr. Odetti), University of Genoa; and the Departments of Neurology (Drs. Cammarata and Ratto) and Human Genetics (Drs. Dagna-Bricarelli, Baldo, and Argusti), Galliera Hospital, Genoa, Italy.

Address correspondence and reprint requests to Dr. Massimo Tabaton, Department of Neurosciences, University of Genoa, Via De Toni 5, 16132 Genoa, Italy; e-mail: mtabaton{at}neurologia.unige.it

Background: Accumulation in the brain of small aggregates of amyloid ß-protein 42 (Aß42) is the major pathogenic event of Alzheimer disease (AD). In familial early-onset AD this event is likely the result of Aß42 overproduction; in the most common sporadic late-onset form of the disease the mechanisms of Aß42 accumulation are unknown.

Methods: To address this issue the authors analyzed plasma levels of Aß42 in 88 elderly patients with amnestic mild cognitive impairment (MCI), chosen as paradigm of preclinical sporadic AD.

Results: The authors found a significant increase of Aß42 plasma levels in women with MCI, in comparison to the affected men and 72 cognitively normal age-matched subjects. The levels were independent of variables in education, apolipoprotein E genotype, cholesterol, and creatinine plasma concentrations, as well as hemoglobin content.

Conclusions: The elevation of Aß42 plasma levels in women with MCI may represent a biologic explanation for the sex-dependent increased incidence of late-onset AD in women identified by epidemiologic studies.

Received January 7, 2004. Accepted in final form April 28, 2004.

*These authors contributed equally to the study.

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