CSF Aβ1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer's disease

The development of validated, qualified, and standardized biomarkers for Alzheimer's disease (AD) that allow for an early presymptomatic diagnosis and discrimination (classification) from other types of dementia and neurodegenerative diseases is warranted to accelerate the successful development of novel disease-modifying therapies. Here, we focus on the value of the 42-residue-long amyloid β isoform (Aβ1-42) peptide in the cerebrospinal fluid as the core, feasible neurobiochemical marker for the amyloidogenic mechanisms in early-onset familial and late-onset sporadic AD. We discuss the role and use of Aβ1-42 in combination with evolving neuroimaging biomarkers in AD detection and diagnosis. Multimodal neuroimaging techniques, directly providing structural-functional-metabolic aspects of brain pathophysiology, are supportive to predict and monitor the progression of the disease. Advances in multimodal neuroimaging provide new insights into brain organization and enable the detection of specific proteins and/or protein aggregates associated with AD. The combination of biomarkers from different methodologies is believed to be of incrementally added risk-value to accurately identify asymptomatic and prodromal individuals who will likely progress to dementia and represent rational biomarker candidates for preventive and symptomatic pharmacological intervention trials.