Biofluid biomarkers in Alzheimer's disease and other neurodegenerative dementias.

Biofluid-based biomarkers have transformed neurodegenerative disease research and care, providing insights into the molecular underpinnings of Alzheimer's disease (AD) and other neurodegenerative dementias. This Review provides an update on recent developments in biofluid-based biomarkers for amyloid-β (Aβ) pathology, tau pathology, neurodegeneration, glial reactivity, α-synuclein pathology, TAR DNA-binding protein 43 (TDP-43) pathology, synaptic pathophysiology and cerebrovascular disease-pathologies and processes that are all relevant to neurodegenerative dementias. Complementing longstanding cerebrospinal assays, improved technologies now facilitate the detection of molecules linked to neurodegenerative brain changes at very low concentrations in the blood. This promises to complement the clinical evaluation of suspected neurodegenerative disease in healthcare with molecular phenotyping biomarkers that will help to link the clinical symptoms to ongoing pathophysiological processes in the brain and improve how patients are referred to specialty clinics for initiation and monitoring of molecularly targeted treatments. Clinically relevant breakthroughs such as the use of anti-Aβ monoclonal antibodies to address Aβ pathology in AD serve as important proof-of-concept examples of how the field is advancing toward molecularly informed prevention and treatment. This Review provides an overview of the most established biofluid-based biomarkers currently in use and offers practical guidance on their interpretation and implementation in clinical settings.