Nordberg A, Scholl M, Carter S, Kadir A, Almkvist O, Ng Y-, Wall A, Engler H, Graff C, Langstrom B.
Biomarkers for following Alzheimer's disease progression. Amyloid 11C-PIB imaging in a multi-tracer paradigm with 11C-d-deprenyl and 18F-FDG studied in preclinial and clinical AD.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Recent progress in molecular imaging provides new knowledge for the understanding of the time course of early
pathological disease processes in Alzheimer's disease (AD). We have observed that 11C-PIB PET can detect
increasing accumulation of fibrillar As in the brains of MCI patients at follow up while more stable levels of fibrillar
As are measured at clinical AD. For understanding of the pathological impact of different forms of As in brain
there is a need for development of PET ligands detecting smaller forms of As, oligomeric forms in brain but also to
understand how synaptic activity and inflammatory processes are related to As pathology. PET fibrillar As imaging
together with CSF biomarkers are promising biomarkers for early recognition of subjects at risk for AD. In a
current longitudinal study, we are enrolling both presymptomatic and symptomatic members of different Swedish
families harboring mutations in the PS1 gene and the 'Swedish' and the 'Arctic' APP gene mutations. We use
the PET tracers 11C-PIB for measuring fibrillar As load, 18F-FDG to investigate cerebral glucose metabolism, and
11C-d-Deprenyl to visualize astrocytosis as a component of neuroinflammatory processes. The subjects also
undergo neuropsychological testing, MRI scan and assays of CSF biomarkers. Cohorts of AD and MCI patients
are studied with the same protocol. Data are analyzed with use of principle component analysis method. Data so
far obtained indicate that increases in As deposition as well as astrocytosis occur early in brain at presymptomatic
stages of AD but the time course of changes as well as brain regions afflicted differ between PET tracers reflecting
the complexity of AD pathology. These studies are important for future drug trials in presymptomatic AD.
References: Nordberg et al. Nature Reviews Neurology 2010; Kadir et al. Neurobiol Aging 2010; Scholl et al. 2009;
Kadir, Nordberg. J Nucl Med 2010; 51: 1418-1430; Kadir Marutle et al. Brain in press.