Imaging the progression of Alzheimer pathology through the brain.
Soon after the widespread availability of computerized x-ray tomography (CT) in clinical medicine in the 1970s, reports began to appear of the changes in the brain in patients with Alzheimer's disease (AD). Atrophy of brain tissue was a common finding, but a critical review in 1990 concluded that “at present there is little definite evidence for clear anatomic brain changes that accurately predict the cognitive dysfunction within a group of patients suffering with AD” (1). Since then, convincing evidence that selective atrophy of particular brain regions is highly correlated with cognitive deficits characteristic of AD has been obtained. What has caused this revolution? First, it has been recognized that the diagnosis of AD was not sufficiently accurate in many early neuroimaging studies. Second, until pioneering studies from New York University (2), most early work did not examine the medial temporal lobe (MTL), the part of the brain with the highest density of AD histopathological markers (amyloid plaques and neurofibrillary tangles) (Fig. (Fig.1).1). In 1992 a CT study of patients with AD, whose diagnosis was later confirmed by histopathology, showed marked atrophy of the MTL (3). Third, there were few longitudinal studies to reveal changes in the same patients over time. One of these, however, showed rapid enlargement of the fluid-filled ventricles in the brain in patients with AD (4). Enlargement of the ventricles is usually caused by loss of brain tissue. A dramatic loss of tissue from the MTL, part of which shrunk at a rate of 15% per year, was found in serial CT studies on patients with AD (5). Because the MTL in controls only shrunk at one-tenth of this rate, it was concluded that AD cannot be the result of an acceleration of normal aging, but must be the consequence of a disease process. The article by Scahill et al. (6) in this issue of PNAS takes the story into a new chapter by using serial MRI scans in patients with AD to show how the disease process, revealed by regional atrophy, spreads in a highly specific way from the MTL to other parts of the brain.
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4135-7.