Journal Article Journal Article Ppublish 6 citations
PubMed: 39353147 DOI: 10.1212/WNL.0000000000209884
Challenges in a Biological Definition of Alzheimer Disease.
Neurology 103(9):e209884
Authors: Jemma Hazan, Kathy Y Liu, Harry Costello, Jeremy D Isaacs, Madhav Thambisetty, Robert Howard
Affiliations
- From the University College London (J.H. K.Y.L. H.C. R.H.); Neuroscience & Cell Biology Research Institute (J.D.I.), St George's, University of London, United Kingdom; and Clinical and Translational Neuroscience Section (M.T.), National Institutes of Health, Bethesda, MD; Laboratory of Behavioral Neuroscience (M.T.), National Institute on Aging, Baltimore, MD.
Abstract
It has been suggested that the diagnostic landscape of Alzheimer disease (AD) is undergoing a profound transformation, marked by a shift toward a biomarker-based approach, as proposed by the Revised Criteria for Diagnosis and Staging of Alzheimer's Disease. These criteria advocate for diagnosing AD solely on biomarkers, without requiring clinical symptoms. This article explores the drivers behind this transition, primarily influenced by the Food and Drug Administration's approval of amyloid-lowering treatments. We evaluate the proposed criteria, which allow for an AD diagnosis based on amyloid "A" or phosphorylated tau "T1" positivity through surrogate amyloid PET imaging, CSF, or plasma biomarkers, and consider the arguments for and against their use. The merits of the new criteria include a clearer definition of AD, which is currently used interchangeably to refer to both the presence of neuropathology and the clinical syndrome. We argue that a purely biological definition risks a category error and emphasize the need for longitudinal data to establish the lifetime risk of dementia in amyloid-positive and tau-positive individuals. We also caution against limiting the scope of biomarker-based AD diagnosis to amyloid and tau alone. In conclusion, we recommend that the criteria remain within the research domain for the present while advocating for the considered adoption of plasma biomarkers in clinical practice.
MeSH
Alzheimer Disease, Biomarkers, Signs And Symptoms, Diagnosis, Amyloid, Neurology, Plasma