Researchers from the Karolinska Institute in Stockholm, Sweden, report in last month’s issue of the journal Brain, on the postmortem examination of the first-ever person with Alzheimer’s to be followed prospectively by positron emission tomography using Pittsburgh Compound B (PIB-PET), which allows visualization of amyloid plaques.
They analyzed the brain of a woman with Alzheimer’s who had volunteered for the first PET-PIB scan ever performed. She received an additional PIB scan two years later, and three PET scans using fluorodeoxyglucose (FDG), a marker for glucose use and therefore brain metabolism. Over the eight years she was studied, the woman’s score on the Mini-Mental State Examination declined from a near-normal score of 27 down to five. The FDG PET scan data showed that her brain’s glucose metabolism decreased in parallel with her cognitive abilities. By contrast, the amyloid signal as seen by PIB PET, already high at first examination, showed little change over two years during which her cognition declined steeply. This pattern matches data from other recent studies, in which amyloid deposits in the brain increase during the mild cognitive impairment (MCI) stage of Alzheimer’s, but seem to plateau during the dementia stage of Alzheimer’s.
Postmortem examination confirmed the patient’s diagnosis of pure Alzheimer’s disease. Interestingly, the researchers found that the density of a certain receptor in the brain, which binds to acetylcholine, and known to be involved in learning and memory, was lower in brain regions with the highest amyloid, suggesting an interaction.
This study provides further evidence that amyloid deposits appear to reach a plateau early in the disease course, when patients experience very mild symptoms or no symptoms at all. Moreover, it suggests that amyloid may be negatively affecting receptors involved in learning and memory, before it has deposited into plaques.