The Dichotomy of Alzheimer's Disease Pathology: Amyloid-β and Tau

In this issue, an article by Tiepolt et al. shows that PET scanning using [C-11]PiB can demonstrate both cerebral blood flow (CBF) changes and amyloid-beta (A beta) deposition in patients with mild cognitive dysfunction or mild dementia of Alzheimer's disease (AD). The CBF changes can be determined because the early scan counts (1-9 minutes) reflect the flow of the radiotracer in the blood passing through the brain, while the A beta levels are measured by later scan counts (40-70 minutes) after the radiotracer has been cleared from regions to which the radiotracer did not bind. Thus, two different diagnostic measures are obtained with a single injection. Unexpectedly, the mild patients with A beta positivity had scan data with only a weak relationship to memory, while the relationships to executive function and language function were relatively strong. This divergence of findings from studies of severely impaired patients highlights the importance of determining how AD pathology affects the brain. A possibility suggested in this commentary is that A beta deposits occur early in AD and specifically in critical areas of the neocortex affected only later by the neurofibrillary pathology indicating a different role of the amyloid-beta protein precursor (A beta PP) in the development of those neocortical regions, and a separate component of AD pathology may selectively impact functions of these neocortical regions. The effects of adverse A beta PP metabolism in the medial temporal and brainstem regions occur later possibly because of different developmental issues, and the later, different pathology is clearly more cognitively and socially devastating.