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PRE-RECORDED: OPPORTUNITIES TO UPDATE THE NIA AA RESEARCH FRAMEWORK IN THE PLASMA BIOMARKER ERA
Abstract
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. Both plasma Ab42/40, particularly mass spec methods, and pTau perform well diagnostically against clinical, PET, CSF or autopsy standards. Most of these data, however, were generated from highly selected samples.
Conclusions: Due to advances in plasma biomarkers, widespread application of a biological definition of AD and AT(N) biomarker phenotyping now seems possible. This has significant implications for design of clinical trials, observational research, and clinical care. However, 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. In particular, it is less clear how well plasma biomarkers perform at the earliest, most subtle stages of disease progression, and in community settings.