Three fundamental issues about Alzheimer’s:
” It has been known for years that Alzheimer ‘s disease in a region of the brain called the entorhinal cortex, ” said co -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 living patients starting specifically in the lateral entorhinal cortex , or LEC . LEC is considered a gateway to the hippocampus, which plays a key role in the consolidation of long memory term , among other functions. If the LEC is affected, also affected other aspects of the hippocampus. ”
With time , spreads Alzheimer LEC directly to other areas of the cerebral cortex , in particular the parietal cortex , a brain region involved in various functions including spatial orientation and navigation. Researchers suspect that Alzheimer “functionally ” , ie , to compromise 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 a LEC impairment when changes in tau and amyloid precursor protein (APP ) co -exist occurs . ” The LEC is especially vulnerable to Alzheimer ‘s disease because it typically 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 disease ” said lead co -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 Psychiatric Institute of the State of New York.
Researchers used a high-resolution variant of functional magnetic resonance imaging to map metabolic defects in the brains of 96 adults who participated in the Project Aging Washington Heights – Inwood Columbia ( WHICAP ) . All adults were free of dementia at the time of registration.
” Study Dr. Richard Mayeux WHICAP 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 early , preclinical phase. ”
The 96 adults were followed for an average of 3.5 years , at which time 12 individuals who have progressed to mild Alzheimer’s disease were found. An analysis of functional magnetic resonance basis of these 12 individuals found a significant decrease in cerebral blood volume ( CBV ) – A measure of the metabolic activity of the LEC – compared to the 84 adults who were free of dementia.
A second part of the study the role of tau and APP was addressed in the LEC dysfunction. While previous studies have suggested that dysfunction of the entorhinal cortex is associated with abnormalities in both tau and APP , it was not known how these proteins interact to drive this dysfunction , particularly in preclinical Alzheimer .
To answer this question , explained first author Usman Khan, a MD- PhD student from the laboratory of Dr. Small , the team created three mouse models , one with elevated levels of tau in the LEC , one with high levels APP , and one with high levels of both proteins. The researchers found that the LEC dysfunction occurred only in mice with both tau and APP .
The study has implications for both research and treatment. ” Now that we have established clearly where Alzheimer’s begins , and showed us that these changes are observable by fMRI, we may be able to detect Alzheimer’s disease at an early preclinical stage , when the disease may be treatable and before spreading to other regions of the brain , “said Dr. Small. In addition , the researchers say , the new imaging method could be used to evaluate the effectiveness of promising drugs during early Alzheimer ‘s disease .
The paper is entitled ” Molecular conductors and lateral entorhinal cortex dysfunction in preclinical Alzheimer ‘s disease cortical spreading . ” Other contributors are Li Liu, Frank Provenzano, Diego Berman, Caterina Profaci , Richard Sloan and Richard Mayeux , all CUMC .