Abstract Body

Aims: In 2018 a workgroup commissioned by the National Institute on Aging and Alzheimer’s Association (NIA-AA) published a research framework in which Alzheimer’s disease (AD) is defined by the underlying pathologic processes rather than by the presence of an etiologically non-specific syndrome or syndromes. This shifts the definition of AD from a syndromal to a biological construct.

Methods: The research framework addresses both diagnosis (definition) and staging of AD. Biomarker and cognitive staging are performed independently from each other. AD can be documented by post-mortem examination or in vivo by biomarkers. Biomarkers are grouped into those of β-amyloid deposition, pathologic tau, and neurodegeneration (AT(N). Both imaging and biofluid (CSF and plasma) biomarkers exist within each AT(N) group.

Results: Since publication of the research framework, significant advances have occurred in development of plasma AT(N) biomarkers. As a results widespread application of a biological definition of AD and AT(N) biomarker phenotyping now seem possible. This has significant implications for design of clinical trials, observational research and clinical care.

Conclusions: Many unanswered questions exist concerning the appropriate roles and the interplay between traditional expensive or invasive AD biomarkers (CSF and imaging) and newer plasma biomarkers.