New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer's disease.

Cerebrospinal fluid (CSF) biomarkers based on the core pathological proteins associated with Alzheimer’s disease (AD), i.e., amyloid-β (Aβ) and tau protein, are widely regarded as useful diagnostic biomarkers. However, a lack of biomarkers for monitoring the treatment response and indexing clinical severity has proven to be problematic in drug trials targeting Aβ. Therefore, new biomarkers are needed to track non-Aβ and non-tau pathology. Many proteins involved in the pathophysiological progression of AD have shown promise as new biomarkers. Neurodegeneration- and synapse-related biomarkers in CSF (e.g., neurofilament light polypeptide [NFL], neurogranin, and visinin-like protein 1) and blood (e.g., NFL) aid prediction of AD progress, as well as early diagnosis. Neuroinflammation, lipid dysmetabolism, and impaired protein clearance are considered important components of AD pathophysiology. Inflammation-related proteins in the CSF, such as progranulin, intercellular adhesion molecule 1, and chitinase-3-like protein 1 (YKL-40), are useful for the early detection of AD and can represent clinical severity. Several lipid metabolism-associated biomarkers and protein clearance-linked markers have also been suggested as candidate AD biomarkers. Combinations of subsets of new biomarkers enhance their utility in terms of broadly characterizing AD-associated pathological changes, thereby facilitating precise selection of susceptible patients and comprehensive monitoring of the treatment response. This approach could facilitate the development of effective treatments for AD. Finding new biomarkers for Alzheimer’s disease (AD) may help in tracking disease progression and identifying optimal patient-specific treatments. Although useful markers are available for diagnosis of AD, they are unreliable for tracking disease progression. Looking for better ways to track disease progression, Sun Ah Park at the Ajou University School of Medicine, Suwon, South Korea, and coworkers have reviewed alternative AD markers. They report that several markers for axonal degeneration, synaptic loss, brain inflammation and lipid metabolism show promise for tracking AD. Some of these markers can be obtained from blood samples, which are minimally invasive to collect. Use of combinations of markers is especially promising for estimating a patient’s disease stage. These results will contribute to developing tailored treatments for this common cause of dementia.