Rapid Progress Toward Reliable Blood Tests for Alzheimer Disease

One of the most important advances in Alzheimer disease (AD) clinical research in the past 2 decades has been the development of biomarkers that detect amyloid-β (Aβ) plaques and tau neurofibrillary tangles in vivo with cerebrospinal fluid (CSF) assays or positron emission tomography (PET). Coupled with imaging or fluid-based markers of brain structural and functional integrity, these biomarkers allow researchers to capture the 3 key features of AD: amyloid plaques, tau neurofibrillary tangles, and neurodegeneration in living people (Figure). One of the most important insights from biomarker studies in AD is the existence of a prolonged preclinical stage spanning 2 decades, during which plaques and tangles deposit in the brain without leading to cognitive symptoms or functional decline. Individuals with preclinical biomarker changes are at risk for cognitive decline and may thus be excellent candidates for early intervention with disease-modifying therapies. The “biomarker revolution” in AD has culminated in the National Institute on Aging–Alzheimer Association Research Framework, which reconceptualizes AD as a biologic entity that is defined entirely by amyloid, tau, and neurodegeneration [AT(N)] biomarkers irrespective of clinical symptoms or functional decline.

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