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A Possible Predictor of Alzheimer Disease

Domenico Praticò, MD; Christopher M. Clark, MD; Feyan Liun, MD; Virginia Y.-M. Lee, PhD; John Q. Trojanowski, MD, PhD

Arch Neurol. 2002;59:972-976.

Background  The isoprostane 8,12-iso-iPF₂-VI, a specific marker of in vivo lipid peroxidation, is increased in Alzheimer disease (AD). The pathological changes associated with AD have a long silent phase before the appearance of clinical symptoms. Several studies have shown that AD is preceded by a prodromal phase characterized by mild cognitive impairment (MCI).

Objective  To investigate levels of this biomarker in subjects with MCI.

Design and Main Outcome Measures  Using gas chromatography–mass spectrometry analysis, we measured 8,12-iso-iPF₂-VI levels in urine, plasma, and cerebrospinal fluid of patients with AD, subjects with MCI, and cognitively normal elderly subjects.

Setting and Patients  Subjects attending the Memory Disorders Clinic.

Results  We found significantly higher 8,12-iso-iPF₂-VI levels in cerebrospinal fluid, plasma, and urine of subjects with MCI compared with cognitively normal elderly subjects.

Conclusions  These results imply that individuals with MCI have increased brain oxidative damage before the onset of symptomatic dementia. Measurement of this isoprostane may identify a subgroup of patients with MCI with increased lipid peroxidation who are at increased risk to progress to symptomatic AD.

From the Center for Experimental Therapeutics and Department of Pharmacology (Drs Praticò and Liun), Department of Neurology (Dr Clark), Center for Neurodegenerative Disease Research (Drs Lee and Trojanowski), and Alzheimer's Disease Center (Drs Clark, Lee, and Trojanowski), University of Pennsylvania School of Medicine, Philadelphia.

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