Two independent laboratories -- one at Columbia University; the other, at Harvard Medical School -- have devised a clever set of experiments to prove that the pathology that leads to tangle formation in Alzheimer disease (AD) spreads across the brain from neuron to neuron rather than selectively hitting vulnerable regions at different time points over the course of the disease.
The finding answers a pivotal question as to how AD progresses, and could open the door to novel treatments that could stop the disease from spreading and damaging key cognitive circuits.
Karen Duff, PhD, Scott Small, MD, and their colleagues at Columbia reported their finding on Feb. 1 in the open-access journal PLoS One and Bradley Hyman, MD, PhD, and his team at Harvard published similar results in the Feb. 23 issue of Neuron.
It's been known since the 1980s that the entorhinal cortex is the first brain region to develop the neurofibrillary tangle pathology of AD. To scientists studying Alzheimer's dementia, this made sense: The entorhinal cortex has major projections to the hippocampus and other memory circuits, and tangle formation is most closely associated with cognitive decline. As the disease progresses and symptoms worsen, the pathology appears to spread from the original site in the entorhinal cortex to many other brain regions.
Until these recent studies, however, no one was quite sure how the disease makes its way across the brain. There were two alternating hypotheses that generated a lot of theories over the decades.