Study shows Alzheimer's disease may spread by 'jumping' from one brain region to another

February 1, 2012

For decades, researchers have debated whether Alzheimer's disease starts independently in vulnerable brain regions at different times, or if it begins in one region and then spreads to neuroanatomically connected areas. A new study by Columbia University Medical Center (CUMC) researchers strongly supports the latter, demonstrating that abnormal tau protein, a key feature of the neurofibrillary tangles seen in the brains of those with Alzheimer's, propagates along linked brain circuits, "jumping" from neuron to neuron.

The findings, published today in the online journal , open new opportunities for gaining a greater understanding of Alzheimer's disease and other neurological diseases and for developing therapies to halt its progression, according to senior author Karen E. Duff, PhD, professor of pathology (in psychiatry and in the Taub Institute for Research on Alzheimer's Disease and the ) at and at the New York State Psychiatric Institute.

Alzheimer's disease, the most common form of dementia, is characterized by the accumulation of plaques (composed of amyloid-beta protein) and fibrous tangles (composed of abnormal tau) in called neurons. Postmortem studies of and neuroimaging studies have suggested that the disease, especially the neurofibrillary tangle pathology, begins in the entorhinal cortex, which plays a key role in memory. Then as Alzheimer's progresses, the disease appears in anatomically linked higher .

"Earlier research, including functional MRI studies in humans, have also supported this pattern of spread," said study coauthor Scott A. Small, MD, professor of neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at CUMC. "But these various findings do not definitively show that Alzheimer's spreads directly from one brain region to another."

To look further into this issue, the CUMC researchers developed a novel in which the gene for abnormal human tau is expressed predominantly in the entorhinal cortex. The brains of the mice were analyzed at different time points over 22 months to map the spread of abnormal .

The researchers found that as the mice aged, the abnormal human tau spread along a linked anatomical pathway, from the entorhinal cortex to the hippocampus to the neocortex. "This pattern very much follows the staging that we see at the earliest stages of human Alzheimer's disease," said Dr. Duff.

The researchers also found evidence suggesting that the abnormal tau protein was moving from neuron to neuron across synapses, the junctions that these cells use to communicate with each other.

The findings of the study have important implications for therapy.

"If, as our data suggest, tau pathology starts in the and emanates from there, the most effective approach may be to treat Alzheimer's the way we treat cancer—through early detection and treatment, before it has a chance to spread," said Dr. Small. "The best way to cure Alzheimer's may be to identify and treat it when it is just beginning, to halt progression. It is during this early stage that the disease will be most amenable to treatment. That is the exciting clinical promise down the road."

Treatments could conceivably target tau during it extracellular phase, as it moves from cell to cell, added Dr. Duff. "If we can find the mechanism by which tau spreads from one cell to another, we could potentially stop it from jumping across the synapses — perhaps using some type of immunotherapy. This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia."

Explore further: Alzheimer's vaccine cures memory of mice

More information: The paper is titled, "Trans-synaptic Spread of Tau Pathology in vivo."

Related Stories

Alzheimer's vaccine cures memory of mice

December 9, 2011

(Medical Xpress) -- A vaccine that slows the progression of Alzheimer's disease and other types of dementia has been developed by researchers at the University of Sydney's Brain and Mind Research Institute (BMRI).

Alzheimer's protein detected in brain fluid of healthy mice

September 21, 2011

(Medical Xpress) -- One of the most promising markers of Alzheimer’s disease, previously thought only to be inside nerve cells, now appears to be normally released from nerve cells throughout life, according to researchers ...

Recommended for you

Neuro chip records brain cell activity

October 26, 2016

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large ...

After blindness, the adult brain can learn to see again

October 25, 2016

More than 40 million people worldwide are blind, and many of them reach this condition after many years of slow and progressive retinal degeneration. The development of sophisticated prostheses or new light-responsive elements, ...

The current state of psychobiotics

October 25, 2016

Now that we know that gut bacteria can speak to the brain—in ways that affect our mood, our appetite, and even our circadian rhythms—the next challenge for scientists is to control this communication. The science of psychobiotics, ...

Can a brain-computer interface convert your thoughts to text?

October 25, 2016

Ever wonder what it would be like if a device could decode your thoughts into actual speech or written words? While this might enhance the capabilities of already existing speech interfaces with devices, it could be a potential ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.