Aggregate binding — amyloid and tau
The target is not a receptor or an enzyme but a shape: the regularly repeating β-pleated sheet of a protein aggregate. That is why one chemical class binds several different misfolded proteins, and why separating amyloid from tau has to be engineered in.
These scans are read by grey–white contrast rather than by intensity. A negative scan keeps a crisp boundary, with binding confined to white matter; a positive scan loses it as cortical grey fills in. Nonspecific white-matter binding is normal and expected, and misreading it as cortical signal is the commonest error.
Interpretation has to stay honest about what positivity means. Between a quarter and a third of cognitively normal 75-year-olds are amyloid-positive — and the figure climbs steeply with age — so a positive scan establishes pathology, not dementia. A negative scan is the more decisive result: it effectively excludes Alzheimer disease. Tau does better as a marker of stage, because neocortical spread tracks Braak staging and correlates with symptom severity far more closely than amyloid burden does.
The agents
F-18 florbetapir / florbetaben / flutemetamolAmyvid · Neuraceq · Vizamyl
PETF-18 · t½ 110 min · uptake 30–90 min depending on agent
- Handle
- Fibrillar β-amyloid plaque
- Trapping
- Lipophilic molecules that cross the BBB and bind the β-pleated sheet of aggregated Aβ. Read by cortical grey–white contrast, not by SUV.
- Use
- Establishing amyloid pathology in cognitive impairment; confirming amyloid positivity before anti-amyloid antibody therapy and monitoring plaque clearance on treatment, for which supplemental indications have been approved.
- Pitfall
- Between a quarter and a third of cognitively normal 75-year-olds are positive — a positive scan establishes pathology, not dementia. Nonspecific white-matter binding is normal and is the main source of reader error. Does not separate Alzheimer disease from cerebral amyloid angiopathy or from dementia with Lewy bodies, which frequently coexist.
C-11 PiBPittsburgh compound B
PETC-11 · t½ 20.4 min
- Handle
- Fibrillar β-amyloid
- Trapping
- The research prototype from which the F-18 agents were derived; excellent contrast.
- Use
- Amyloid research and quantitative studies.
- Pitfall
- The 20-minute half-life restricts it to cyclotron sites, which is precisely why the F-18 analogues were developed.
F-18 flortaucipirTauvid
PETF-18 · t½ 110 min · approved 2020
- Handle
- Paired helical filament tau (3R/4R, Alzheimer type)
- Trapping
- Binds aggregated tau. Neocortical spread follows Braak staging and correlates with symptom severity far better than amyloid burden.
- Use
- Estimating the density and distribution of tau pathology in adults evaluated for Alzheimer disease.
- Pitfall
- Off-target binding in choroid plexus, basal ganglia and neuromelanin-containing and MAO-B sites — choroid plexus signal is the classic problem for medial temporal reads. Poor affinity for the non-Alzheimer 4R tauopathies such as PSP and CBD, so a negative scan does not exclude them.
F-18 florquinitauTauklarify (MK-6240)
PETF-18 · t½ 110 min · approved August 2026
- Handle
- Paired helical filament tau
- Trapping
- Higher affinity than flortaucipir with markedly less off-target binding, particularly in the choroid plexus.
- Use
- Tau PET in adults with cognitive impairment under evaluation for Alzheimer disease; the cleaner medial temporal read is its main advantage.
- Pitfall
- Newly approved, so normal databases, reader training and reimbursement pathways are still maturing. It shares the class limitation of poor binding to non-Alzheimer tauopathies.