Finding a pathological diagnosis for Alzheimer's disease: Are inflammatory molecules the answer?

Conventional diagnostic tools for Alzheimer's disease (AD) are currently based on a number of clinical criteria, and a definitive diagnosis still relies on pathological evaluation at autopsy. Moreover, neurodegenerative changes are believed to begin years before clinical presentation. There is therefore an essential need for a reliable AD biomarker to aid in the identification of preclinical disease, early diagnosis, prediction of disease progression and treatment response. There is mounting evidence that chronic inflammatory processes play a fundamental role in the progression of neuropathological changes in AD. Clinical and experimental evidence supports the involvement of inflammatory changes in the early stages of AD, even before the appearance of amyloid deposits. Therefore biomarkers that reflect the inflammatory process in AD hold promise. Tests based on these should preferably be reliable, noninvasive and costeffective, which has led to an increasing focus on the use of blood-based biomarkers. This review considers the current progress in AD inflammatory biomarker research followed by a detailed analysis of two leading putative inflammatory biomarkers: a-2-macroglobulin and clusterin.