For decades, researchers have debated whether Alzheimer's disease starts independently in vulnerable brain regions at different times, or if it begins in one region and then spreads to neuroanatomically connected areas. A new study by Columbia University Medical Center (CUMC) researchers strongly supports the latter, demonstrating that abnormal tau protein, a key feature of the neurofibrillary tangles seen in the brains of those with Alzheimer's, propagates along linked brain circuits, "jumping" from neuron to neuron.
The findings, published today in the online journal PloS One, open new opportunities for gaining a greater understanding of Alzheimer's disease and other neurological diseases and for developing therapies to halt its progression, according to senior author Karen E. Duff, PhD, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.
Alzheimer's disease, the most common form of dementia, is characterized by the accumulation of plaques (composed of amyloid-beta protein) and fibrous tangles (composed of abnormal tau) in brain cells called neurons. Postmortem studies of human brains and neuroimaging studies have suggested that the disease, especially the neurofibrillary tangle pathology, begins in the entorhinal cortex, which plays a key role in memory. Then as Alzheimer's progresses, the disease appears in anatomically linked higher brain regions.
"Earlier research, including functional MRI studies in humans, have also supported this pattern of spread," said study coauthor Scott A. Small, MD, professor of neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at CUMC. "But these various findings do not definitively show that Alzheimer's spreads directly from one brain region to another."
To look further into this issue, the CUMC researchers developed a novel transgenic mouse in which the gene for abnormal human tau is expressed predominantly in the entorhinal cortex. The brains of the mice were analyzed at different time points over 22 months to map the spread of abnormal tau protein.