Amyloid beta plaques

Amyloid beta is a peptide, cleaved from the amyloid precursor protein, that misfolds and aggregates into extracellular neuritic plaques, one of the two neuropathological hallmarks of Alzheimer's disease (the other being tau neurofibrillary tangles). PET tracers such as 18F-florbetapir bind fibrillar amyloid aggregates with nanomolar affinity (Kd approximately 3.7 nM for florbetapir) and do not appreciably bind tau, so they read out plaque burden rather than tangle burden.

Florbetapir (Amyvid) was FDA-approved in 2012 for PET imaging to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease; its label was updated in June 2025 to add selection of patients for amyloid-targeting therapy, reflecting the arrival of anti-amyloid antibody drugs whose eligibility and monitoring depend on amyloid PET or blood biomarkers. Other approved 18F amyloid tracers include florbetaben (Neuraceq) and flutemetamol (Vizamyl); all three are stilbene or benzothiazole derivatives related to the original 11C-Pittsburgh compound B.

As an imaging target, amyloid's strength is that a negative scan has high negative predictive value (sparse or no plaque makes an Alzheimer's diagnosis unlikely), which is clinically decisive. Its main limitation is specificity for a diagnosis: a positive scan indicates plaque is present but this can also occur in cognitively normal older adults and in other neurodegenerative conditions, so a positive result does not by itself confirm Alzheimer's disease, and none of the approved tracers is validated to monitor treatment response or to predict conversion to dementia.