If Alzheimer’s disease begins ;
ROOTS OF ALZHEIMER:
Researchers at Columbia University have identified 3 discoveries about Alzheimer:
Learn why this may help researchers treat Alzheimer’s before and better.
Alzheimer’s disease begins in the entorhinal cortex (yellow). Using functional magnetic resonance imaging in the mouse (left) and human brain (right), researchers provide evidence that the disease spreads from the entohrinal cortex (yellow) to the other (red) cortical regions – and the posterior parietal cortex perirhinal cortex . (Credit :. Usman Khan / laboratory Scott A. Small, MD, Columbia University Medical Center)
“It has been known for years that Alzheimer’s disease begins in a brain region known as the entorhinal cortex, “said co-lead author Scott A. Small, MD, Boris Katz and Rose professor of Neurology, professor of radiology and director of the Alzheimer’s disease Research Center. “But this study is the first to show in patients that begins specifically in the lateral entorhinal cortex, or LEC alive. The LEC is considered a gateway to the hippocampus, which plays a key role in consolidating memory long term, among other functions. If the LEC is affected also affected other aspects of the hippocampus. ”
study also shows that, over time, spreads Alzheimer’s LEC directly to other areas of the cerebral cortex, particularly the parietal cortex, a brain region involved in various functions, including spatial orientation and the navegation. Researchers suspect that Alzheimer’s disease “functionally”, ie, by compromising the function of neurons in the LEC, which in turn threatens the integrity of neurons in adjacent areas spreads.
A third important finding of the study is that LEC dysfunction occurs when changes in the tau and amyloid precursor (APP) protein coexist. “The LEC is especially vulnerable to Alzheimer’s disease, as they usually tau, which sensitizes the LEC to the accumulation of APP accumulates. Together, these two proteins damage neurons in the LEC, setting the stage for disease Alzheimer “said co-lead 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 the Institute of psychiatry at New York State.
in the study, the researchers used a high-resolution version of functional magnetic resonance imaging to map brain metabolic defects in 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP). All adults were free of dementia at the time of registration.
“WHICAP study by Dr.. Richard Mayeux allows us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer’s disease,” said Dr. Small. “This study has given us a unique opportunity to image and characterize patients with Alzheimer’s disease in its earliest, pre-clinical stage.”
The 96 adults were followed for a mean of 3.5 years, at which time 12 individuals to have progressed to mild Alzheimer’s disease were found. An analysis of functional magnetic resonance baseline of 12 individuals found a significant decrease in cerebral blood volume (CBV) – a measure of the metabolic activity -. In the LEC compared with the 84 adults who were free of dementia
A second part of the study addressed the role of tau and APP in the LEC dysfunction. While previous studies have suggested that the entorhinal cortex dysfunction is associated with both tau and APP anomalies, it was not known how these proteins interact to lead this dysfunction, particularly in pre-clinical Alzheimer’s.
To answer this question, the first author Usman Khan, a doctoral student in the MD-based laboratory of Dr. Small, the team created three models of mice, one with high levels of tau explained LEC, one with high levels of APP, and one with high levels of both proteins. The researchers found that LEC dysfunction occurred only in mice with both tau and APP.
The study has implications for both research and treatment. “Now that we have identified where starts Alzheimer’s disease, and showed that these changes are observable by functional magnetic resonance imaging, which may be able to detect Alzheimer’s disease in its preclinical phase earlier, when the disease may be more treatable and before it spreads to other brain regions, “said Dr. Small. In addition, the researchers say, the new imaging method could be used to assess the effectiveness of promising Alzheimer drugs during the early stages of the disease.
The study is titled “Molecular conductors and dissemination of cortical dysfunction lateral entorhinal cortex in preclinical Alzheimer’s disease.” The other contributors are Li Liu, Frank Provenzano, Diego Berman, Caterina Profaci, Richard Sloan and Richard Mayeux, all at CUMC.
The study was supported by grants from the National Institutes of Health (AG034618, AG025161, AG07232, AG037212, NS074874, and HL094423
Columbia University Medical Center , via Newswise.
This article was originally published on alzheimersweekly, Read the original article here