Increase of Brain Oxidative Stress in Mild Cognitive Impairment

TLDR

Alzheimer disease is characterized by elevated lipid‑peroxidation marker 8,12‑iso‑iPF2α‑VI and a prolonged silent phase, with mild cognitive impairment recognized as a prodromal stage. The study aimed to assess 8,12‑iso‑iPF2α‑VI levels in individuals with mild cognitive impairment. Using gas‑chromatography mass‑spectrometry, the authors quantified 8,12‑iso‑iPF2α‑VI in urine, plasma, and cerebrospinal fluid from AD patients, MCI subjects, and cognitively normal elderly at a memory disorders clinic. MCI participants exhibited markedly higher 8,12‑iso‑iPF2α‑VI in all fluids compared to controls, indicating increased brain oxidative damage before dementia onset and suggesting the marker could identify high‑risk MCI patients.

Abstract

<h3>Background</h3> The isoprostane 8,12-<i>iso</i>-iPF_2α-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). <h3>Objective</h3> To investigate levels of this biomarker in subjects with MCI. <h3>Design and Main Outcome Measures</h3> Using gas chromatography–mass spectrometry analysis, we measured 8,12-<i>iso</i>-iPF_2α-VI levels in urine, plasma, and cerebrospinal fluid of patients with AD, subjects with MCI, and cognitively normal elderly subjects. <h3>Setting and Patients</h3> Subjects attending the Memory Disorders Clinic. <h3>Results</h3> We found significantly higher 8,12-<i>iso</i>-iPF_2α-VI levels in cerebrospinal fluid, plasma, and urine of subjects with MCI compared with cognitively normal elderly subjects. <h3>Conclusions</h3> 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.