By using functional MRI, researchers at Columbia University Medical Center have clarified where Alzheimer's disease begins and how it spreads through the brain.
The study, published in the online edition of the journal Nature Neuroscience, found that Alzheimer's originates in the brain region known as the lateral entorhinal cortex.
"It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex," said co-senior author Scott A. Small, M.D., Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer's Disease Research Center, in an announcement. "But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected."
The study involved 96 adults who were followed for an average of 3.5 years. Over the period of the study 12 of those individuals were found to have progressed to mild Alzheimer's disease. Baseline functional MRI images of those 12 found significant decreases of cerebral blood volume, which is an indicator of metabolic activity, in the LEC compared to the 84 individuals who hadn't progressed to Alzheimer's.
The researchers found that over time the disease spreads from the LEC into other areas of the brain involving functions such as spatial orientation and navigation. Another part of the study assessed the role that tau and amyloid precursor protein (APP) play in LEC dysfunction.
"The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's," said co-senior author Karen E. Duff, PhD, professor of pathology and cell biology (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.
The researchers believe the results of the study have implications for both further research and treatment of the disease. "Now that we've pinpointed where Alzheimer's starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer's at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions," said Small.
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