Circulating biomarkers of protein oxidation for Alzheimer disease: Expectations within limits

Alzheimer disease (AD), the most common dementing disorder, is a multifactorial disease with complex etiology. Among different hypotheses proposed for AD one of the most corroborated is the "oxidative stress hypothesis". Although recent studies extensively demonstrated the specific oxidative modification of selected proteins in the brain of AD patients and how their dysfunction possibly correlates with the pathology, there is still an urgent need to extend these findings to peripheral tissue. So far very few studies showed oxidative damage of proteins in peripheral tissues and current findings need to be replicated. Another limit in AD research is represented by the lack of highly specific diagnostic tools for early diagnosis. For a full screening and early diagnosis, biomarkers easily detectable in biological samples, such as blood, are needed. The search of reliable biomarkers for AD in peripheral blood is a great challenge. A few studies described a set of plasma markers that differentiated AD from controls and were shown to be useful in predicting conversion from mild cognitive impairment, which is considered a prodromal stage, to AD. We review the current state of knowledge on peripheral oxidative biomarkers for AD, including proteomics, which might be useful for early diagnosis and prognosis.