Abstract
Ten individuals suspected of having possible Alzheimer disease underwent PET imaging using 18F-Flubetapir. Only one of ten individuals had a pattern typical for normal elderly control subjects with 9 of the 10 showing a Alzheimer type pattern for the cerebral cortex yet all 10 subjects had uniformly low to absent tracer localization to the cerebellar cortex; significantly high tracer activity was noted within the subcortical white matter of the cerebellum in a symmetric manner in all cases. In consideration of studies that have shown amyloid deposits within the cerebellar cortex in 90% of pathologically proven cases of Alzheimer’s disease, these findings raise questions about the actual clinical value of florbetapir PET imaging in evaluating cerebellar involvement and raises questions whether PET imaging of this tracer accurately portrays patterns of amyloid deposition, as there is rapid hepatic metabolism of the parent compound after intravenous injection. Possible links to Alzheimer’s disease related alterations in blood-brain barrier permeability to the parent compound and subsequent radiolabelled metabolites are discussed as potential mechanisms that could explain the associated localization of the tracer to the brainstem and subcortical white matter within the cerebrum and cerebellum of Alzheimer’s disease patients.
Highlights
Alzheimer’s disease is a devastating health problem of an increasing magnitude within the expanding aging population that requires definitive diagnostic methods
Intense activity was consistently seen within the brain stem, which is seemingly inconsistent with the known patterns of amyloid deposition in Alzheimer’s disease
As prior pathologic studies have shown a gradient of A4 beta amyloid activity in Alzheimer’s disease (AD), where more plaques were seen in the midbrain and least in the medulla,[6,7] with healthy controls showing little to no brain stem plaque, the PET scan findings become hard to explain; as explained below, it is hypothesized that 18F-flubetapir metabolites with no specific avidity for amyloid could contribute significantly to the image and appear in the brain stem, related to possible alterations in the blood-brain barrier but this is only hypothetical and not proven in any way
Summary
Alzheimer’s disease is a devastating health problem of an increasing magnitude within the expanding aging population that requires definitive diagnostic methods In this regard, 18F-FDG PET imaging has been proven to be very helpful in identifying areas of focal posterior parietal hypometabolism linked to Alzheimer’s disease (AD); other PET imaging methods include 11C-flumazenil that reveals no loss of benzodiazepine receptors and preservation of the GABAergic neuron population within dysfunctional posterior parietal cortical regions of Alzheimer disease patients.[1,2]. Much interest has been generated on the use of 18F and 11C labeled compounds that bind to amyloid plaque on postmortem brain tissue sections, but generate conflicting data with regards to their in-vivo distribution after intravenous injection to living subjects. Since amyloid plaques are well described in the cerebellum of Alzheimer patients,[5] further investigation was carried out here to understand why there is essentially absent flubetapir tracer activity within the cerebellar cortex
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