Study shows Alzheimer's disease may spread by 'jumping' from one brain region to another
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 PloS One, 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 Aging Brain) at CUMC 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 brain cells called neurons. Postmortem studies of human brains 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 brain regions.
"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 transgenic mouse 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 tau protein.
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 entorhinal cortex and emanates from there, the most effective approach may be to treat Alzheimer's the way we treat cancerthrough 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."
More information: The paper is titled, "Trans-synaptic Spread of Tau Pathology in vivo."
Provided by Columbia University Medical Center
- Alzheimer's vaccine cures memory of mice Dec 09, 2011 | not rated yet | 0
- Cancer-related protein may play key role in Alzheimer's disease Feb 28, 2008 | not rated yet | 0
- Alzheimer's protein detected in brain fluid of healthy mice Sep 21, 2011 | not rated yet | 0
- Alzheimer's: French scientists focus on key target Jan 24, 2012 | not rated yet | 0
- Newly identified genetic marker involved in aggressive Alzheimer's disease Sep 16, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization ...
Neuroscience May 24, 2013 | 4 / 5 (4) | 0
How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.
Neuroscience May 24, 2013 | 4 / 5 (2) | 2
One of the major frontiers of modern science is a comprehensive understanding of the human brain and its functions to guide the development of new technologies in information and communication. In a major announcement for ...
Neuroscience May 24, 2013 | 3.7 / 5 (3) | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
Neuroscience May 23, 2013 | 4.9 / 5 (10) | 0 |
(Medical Xpress)—The human brain is able to identify individuals' voices by comparing them against an internal 'average voice' prototype, according to neuroscientists.
Neuroscience May 23, 2013 | 3.7 / 5 (3) | 3 |
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
15 hours ago | 5 / 5 (2) | 5
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
7 hours ago | not rated yet | 1
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
15 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
15 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
15 hours ago | not rated yet | 0