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

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). To investigate levels of this biomarker in subjects with MCI. 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. Subjects attending the Memory Disorders Clinic. 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. 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.