Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease

BACKGROUND: The isoprostane 8,12-iso-iPF(2alpha)-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-iPF(2alpha)-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-iPF(2alpha)-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.