An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders

Cerebrospinal fluid analyses and neuroimaging can identify the underlying pathophysiology at the earliest stage of some neurodegenerative disorders, but do not have the scalability needed for population screening. Therefore, a blood-based marker for such pathophysiology would have greater utility in a primary care setting and in eligibility screening for clinical trials. Rapid advances in ultra-sensitive assays have enabled the levels of pathological proteins to be measured in blood samples, but research has been predominantly focused on Alzheimer disease (AD). Nonetheless, proteins that were identified as potential blood-based biomarkers for AD, for example, amyloid-β, tau, phosphorylated tau and neurofilament light chain, are likely to be relevant to other neurodegenerative disorders that involve similar pathological processes and could also be useful for the differential diagnosis of clinical symptoms. This Review outlines the neuropathological, clinical, molecular imaging and cerebrospinal fluid features of the most common neurodegenerative disorders outside the AD continuum and gives an overview of the current status of blood-based biomarkers for these disorders. Most research into blood-based biomarkers for neurodegenerative disorders has so far focused on Alzheimer disease. In this Review, Aarsland and colleagues give an overview of the current status of blood-based biomarkers for the non-Alzheimer disease neurodegenerative disorders. Key points Neurodegenerative disorders are characterized by protein aggregation and other pathological processes, which can affect the composition of biofluids such as blood and cerebrospinal fluid (CSF). Analysis of CSF and molecular imaging of the brain enable the stratification of patient populations on the basis of underlying pathology, but are limited as population screening tools. Advances in ultra-sensitive immunoassays for the measurement of amyloid-β, neurofilament light chain, total tau and phosphorylated tau, as well as mass spectrometry-based methods for the measurement of amyloid-β, have demonstrated that a blood-based screening tool for Alzheimer disease is a realistic and plausible possibility. Evidence now suggests that blood-based biomarkers could also be important for other common neurodegenerative disorders: for example, Lewy body dementia, atypical parkinsonian disorders and frontotemporal dementia.