Alzheimer's disease may begin in a particularly vulnerable area of the brain and then further spread its damaging effects to other regions, according to a new study researchers conducted in mice.
The brain region, known as the entorhinal cortex, is part of a circuit that is crucial for memory. Researchers had previously suspected this region was affected early on in Alzheimer's disease.
The new study suggests the plaques — called amyloid-beta peptides, which build up in the brains of patients with Alzheimer's and damage memory — might spread to the rest of this brain from this region.
The finding could help researchers design new therapies for the disease, said study researcher Julie Harris, of the Gladstone Institute of Neurological Disease, in San Francisco.
“One could envision that targeting therapies to the entorhinal cortex early in the disease process could perhaps help stop spread of disease into other connected brain regions,” she said.
The entorhinal cortex is connected to another brain region called the hippocampus, and interference with this connection may contribute to the memory loss seen in the early stages of Alzheimer's, the researchers found.
The proteins found in the brains of those affected with Alzheimer's disease are made from a larger protein called the amyloid precursor protein, or APP. In the study, Harris and her colleagues used mice that had been genetically engineered to produce APP only in the entorhinal cortex. Previous studies have used mice that make APP throughout their brains, which has made it difficult to determine how different brain regions may contribute to the disease, she said.
The mice showed impairments in learning and memory that were similar to the problems seen in mice that produce APP in many brain areas.
The mice also had deposits of amyloid-beta peptide in brain regions that receive input from the entorhinal cortex, Harris said.
The researchers, are planning to carry out future experiments to investigate how the disease progresses from the entorhinal cortex to other regions. And because the study was conducted in mice, further research needs to be done to determine if the results hold true for humans.
The study will be published in the Nov. 4 issue of the journal Neuron.
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