The progression of Alzheimer’s disease could soon be tracked with much greater precision. In a new study from Columbia University Medical Center, researchers clarify three crucial characteristics of the disease: where it originates, why it originates there, and how it spreads to neighboring tissue. The findings could help physicians improve screening protocols and treatment strategies against the neurodegenerative disorder that currently affects upward of five million Americans.

Like Parkinson’s and Huntington’s disease, Alzheimer’s disease is a currently incurable condition characterized by neurodegeneration –– a debilitating syndrome whereby the brain’s nerve connections gradually lose structure and function. However, the exact progression of this syndrome has long been a mystery to the medical community. The new study, which is published in the journal Nature Neuroscience, provides the first-ever description of some of the key characteristics of neurodegeneration. By using functional magnetic resonance imaging (fMRI) to monitor brain activity in 12 individuals diagnosed with mild Alzheimer’s, the research team was able to derive a new, detailed image of the disorder.

"It has been known for years that Alzheimer's starts in a brain region known as the entorhinal cortex," co-senior author Scott A. Small said in a press release. "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."

In addition, the study shows that the LEC allows Alzheimer’s to spread to other areas of the cerebral cortex, particularly the parietal cortex. Impairments in this brain center are thought to account for the difficulties in spatial orientation and navigation that many sufferers exhibit. According to the researchers, this progress is made possible by the condition’s capacity to spread “functionally” –– that is, via a kind of chain reaction that targets the function of neurons.

Finally, the results also explain why Alzheimer’s typically starts in the LEC and not in other cerebral centers. Essentially, the common build-up of tau protein makes the area more susceptible to damage from amyloid precursor protein (APP) –– a molecule associated with neurodegeneration. “The LEC is especially vulnerable to Alzheimer's because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP,” co-senior author Karen E. Duff said. “Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer's."

According to the National Institutes of Health, Alzheimer’s disease currently affects about 44 million people worldwide. Recent projections suggest that improved public health and lifespans will cause this number to triple by 2050. The condition, which is characterized by a gradual loss of nerve functions, usually results in mental decline and an array of cognitive impairments. In turn, these symptoms often bring with them a number of lifestyle changes as well as an increased risk of injuries.

[The current study] enables us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer's disease," Small told reporters. "This study has given us a unique opportunity to image and characterize patients with Alzheimer's in its earliest, preclinical stage."

Source: Khan UA, Liu L, Provenzano FA, Berman DE. "Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease." Nature Neuroscience. 2013.