PET imaging of amyloid in Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of dementia and is characterised by progressive impairment in cognitive function and behaviour. The pathological features of AD include neuritic plaques composed of amyloid-beta peptide (Abeta) fibrils, neurofibrillary tangles of hyperphosphorylated tau, and neurotransmitter deficits. Increases in the concentration of Abeta in the course of the disease with subtle effects on synaptic efficacy will lead to gradual increase in the load of amyloid plaques and progression in cognitive impairment. Direct imaging of amyloid load in patients with AD in vivo would be very useful for the early diagnosis of AD and the development and assessment of new treatment strategies. Three different strategies are being used to develop compounds suitable for in vivo imaging of amyloid deposits in human brains. Monoclonal antibodies against Abeta and peptide fragments have had limited uptake by the brain when tested in patients with AD. When putrescine-gadolinium-Abeta has been injected into transgenic mice overexpressing amyloid, labelling has been observed with MRI. The small molecular approach for amyloid imaging has so far been most successful. The binding of different derivatives of Congo red and thioflavin has been studied in human autopsy brain tissue and in transgenic mice. Two compounds, fluorine-18-labelled-FDDNP and carbon-11-labelled-PIB, both show more binding in the brains of patients with AD than in those of healthy people. Additional compounds will probably be developed that are suitable not only for PET but also for single photon emission CT (SPECT).
Karolinska institute, Neurotec Department, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden. agneta.nordberg@neurotec.ki.se
Agneta
A
Nordberg
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005456:Fluorescent Dyes; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D014055:Tomography, Emission-Computed
D005456:Fluorescent Dyes; D007202:Indicators and Reagents