Alzheimer’s birthplace in the brain announced

The lateral entorhinal cortex has been named the area in the brain where neurodegenerative disease originates, providing new information about how neuronal dysfunction leads to Alzheimer’s progression, according to a study published Dec. 22 in Nature Neuroscience.

Researchers including Usman A. Khan, a PhD candidate at Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York City, pinpointed the spot after studying 96 patients for an average 3.5 years using molecular MRI.

“We used a high-resolution functional magnetic resonance imaging (fMRI) variant that can map metabolic defects in patients and mouse models to address basic questions about entorhinal cortex pathophysiology,” wrote the authors. “The entorhinal cortex is divided into functionally distinct regions, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), and we exploited the high-resolution capabilities of the fMRI variant to ask whether either of them was affected in patients with preclinical Alzheimer's disease.”

The study then delved into the connection between tau and amyloid deposition in this region in mouse models to further clarify if Alzheimer’s disease could be traced back to the lateral entorhinal cortex. 

“We found that the LEC was affected in preclinical disease, that LEC dysfunction could spread to the parietal cortex during preclinical disease and that APP expression potentiated tau toxicity in driving LEC dysfunction, thereby helping to explain regional vulnerability in the disease,” the researchers wrote.