Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Pathologically it is defined by extracellular amyloid-beta neuritic plaques and intracellular tau neurofibrillary tangles, which typically precede clinical symptoms by a decade or more. Clinical diagnosis on history and neuropsychological testing alone is imprecise, particularly in atypical or early presentations, so tissue-level confirmation of amyloid and, increasingly, tau pathology has become part of routine specialist work-up.

Amyloid PET tracers (florbetapir, flutemetamol, florbetaben) and the tau tracer flortaucipir let clinicians see this pathology in a living patient. A negative amyloid scan is strong evidence against AD as the cause of cognitive impairment; a positive scan is consistent with AD but is not diagnostic on its own, since amyloid deposition also occurs in a minority of cognitively normal older adults. The 2024 Alzheimer's Association revised criteria treat a positive amyloid biomarker (PET or CSF) as a 'Core 1' biomarker sufficient, together with clinical context, to support a biological diagnosis of AD, with tau PET as a 'Core 2' biomarker used to stage disease severity.

From 2023 onward the field entered a treatment era: the anti-amyloid monoclonal antibodies lecanemab (Leqembi) and donanemab (Kisunla) received full FDA approval for early symptomatic AD (mild cognitive impairment or mild dementia), and both require documented amyloid pathology, established by PET or CSF, before starting therapy. This has turned amyloid PET from a largely diagnostic-exclusion tool into a gatekeeping test for a treatable population, and serial quantitative amyloid PET (reported in Centiloids) is used by some centres to decide when plaque clearance is sufficient to stop donanemab dosing.