Alzheimer's: where it starts and why

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Three fundamental questions about Alzheimer’s have now been answered: where it starts, why it starts there, and how it spreads. These findings could improve diagnosis as well as treatment of the disease.

fMRI used to reveal Alzheimer’s secrets

“It has been known for years that Alzheimer’s starts in a brain region known as the entorhinal cortex,” explained co-senior author Scott A. Small, MD, Boris and Rose Katz Professor of Neurology, professor radiology, and director of the Alzheimer’s Disease Research Center. “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.”

Spreads by affecting the function of neurons

Over time Alzheimer’s spreads from the LEC directly to other areas of the cerebral cortex. Researchers believe that it spreads “functionally”, that is, by compromising the function of the neurons in the LEC which then compromises the integrity of neurons in adjoining area.

Two proteins come together to damage neurons

LEC dysfunction occurs when changes in tau and amyloid precursor protein (APP) co-exist. “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,” stated co-senior author Karen D. Duff, PhD, professor of pathology and cell biology at CUMC and at the New York State Psychiatric Institute.

The study tracked 96 healthy adults using high-resolution variant of fMRI for 3.5 years. By the end, several of the participants had Alzheimer’s

Better able to detect and treat

“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,” explained Dr. Small. The new imaging method could be used to assess the efficacy of promising drugs during the early stages of the disease.

Soruce: MedicalNewsToday, Nature Neuroscience

 
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