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Evidence of increased oxidative damage in subjects with mild cognitive impairment

From the Departments of Anatomy and Neurobiology (Drs. Keller, Scheff, and Ding), Chemistry (Dr. Butterfield), and Pathology and Neurology (Dr. Markesbery), and Sanders-Brown Center on Aging (Drs. Keller, Schmitt, Scheff, Chen, Butterfield, and Markesbery), University of Kentucky, Lexington.

Address correspondence and reprint requests to Dr. Jeffrey N. Keller, 205 Sanders-Brown Center on Aging, 800 South Limestone, University of Kentucky, Lexington, KY 40536-0230; e-mail: Jnkell0{at}pop.uky.edu

Objective: To determine if increased levels of oxidative damage are present in the brains of persons with mild cognitive impairment (MCI), a condition that often precedes Alzheimer disease (AD).

Methods: The authors assessed the amount of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and malondialdehyde in the superior and middle temporal gyri (SMTG) and cerebellum of short postmortem interval and longitudinally evaluated normal subjects and those with MCI and early AD.

Results: Elevated levels of protein carbonyls (~25%), malondialdehyde (~60%), and TBARS (~210%) were observed in the SMTG of individuals with MCI and early AD vs normal control subjects. The elevation in TBARS was associated with the numbers of neuritic but not diffuse plaques. Levels of protein carbonyls increased as delayed verbal memory performance declined.

Conclusion: Oxidative damage occurs in the brain of subjects with mild cognitive impairment, suggesting that oxidative damage may be one of the earliest events in the onset and progression of Alzheimer disease.

Supported by NIH grants (AG018437, 5P01-AG005119, 5P50-AG05114), and grants from the Hereditary Disease Foundation and the Abercrombie Foundation.

Received September 1, 2004. Accepted in final form December 2, 2004.

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