A protein tangle in an Alzheimer’s-afflicted neuron
Exactly how Alzheimer’s disease proliferates through the brain, overtaking one region after another, has eluded scientists. As the disease progresses, tau—a malformed protein that forms snarls and tangles inside neurons—shows up in more and more brain areas. Researchers have wondered whether tau, and the disease, are working their way out from a single area of origin or mounting numerous, distinct attacks on vulnerable parts of the brain. Two new studies in mice provide strong support for the first idea: Tau seems to pass from affected cells to their neighbors, spreading much the same way a virus or bacteria infection would.
The studies—one recently published in PLoS ONE, the other forthcoming in Neuron—used mice genetically engineered to produce abnormal human tau protein in the entorhinal cortex, the tiny bit of brain tissue where Alzheimer’s first appears in most patients. Since those cells, but not others, were equipped to produce human tau, any tau that showed up elsewhere in the brain could be traced back to the entorhinal cortex. The researchers watched and waited, and found that the tau proteins spread through neural circuits out into other areas—and where tau went, cell death followed, slowly decimating the rodents’ brains.
Human brian imaging studies and autopsies had pointed toward the same answer, but hadn’t been conclusive. These studies in mice provide stronger support for the idea of Alzheimer’s infection-like spread (though unlike many actual viruses, of course, the disease isn’t contagious). What’s more, on the heels of the Obama Administration’s call to treat or prevent Alzheimer’s by 2025, this research points towards an intriguing possibility for treatment: targeting tau before it makes its way to other parts of the brain could perhaps slow or stop the progress of the disease.
Image courtesy of National Institute on Aging / Wikimedia Commons
February 3rd, 2012 at 9:27 am
Interesting article on how Alzheimer’s propagates. However, noticed a typo in 2nd word of last paragraph. “Human brian imaging studies”.
February 3rd, 2012 at 1:33 pm
This is feels very misleading to me…
Alzheimer has always had to do with proteins that are misfolded that propagate further misfolded proteins.
So it makes sense they spread from neighbor to neighbor.
But how is that a metaphor for viruses? Thats not how viruses spread. They either explode in a bundle of viruses, and possibly infect many cells with virus shrapnel, or they replicate infected cells, and populate areas with infected cell (slower).
Maybe…am I misunderstanding the article?
February 3rd, 2012 at 2:27 pm
Aren’t prions a refolded brain protein? And doesn’t it somehow cause other normal brain proteins to reform like it? And it isn’t even a living thing? Didn’t some Canadians doctors do brain autopsies on previously diagnosed “Alzheimers” patientsw (after death) and found it to be really C-Y (human spongiform encepalophy) in them about 6 years ago? What does that tell us?
February 3rd, 2012 at 2:55 pm
Hmm… personally, I thought it was implying the spread of a virus on a human-to-human scale; however, if I am incorrect, you provide an excellent point, Tomek.
February 4th, 2012 at 11:00 pm
Neurons communicate in more ways than chemical neurotransmission. Neurons in a circuit exhange trophic factors and small proteins, like neuropeptides, can diffuse through a circuit. Without reading the paper, this seems to be what they are referring to.
Also, viruses are able to spread along neurons, hence the dermatomal pattern seen in shingles.
February 5th, 2012 at 9:01 am
I’m with Night-Gaunt; this is only half the story and not even the more interesting half. I don’t understand how an article – even a short one – about a misfolded protein propagating itself from neighbor to neighbor and causing the same symptoms that appear in “mad cow disease” and Creutzfeldt–Jakob disease can fail to mention the word “prion” or those other diseases, at least in passing. But still a fascinating result.
February 6th, 2012 at 1:03 am
Interesting read but several questions still remain.
Such as, what is causing the Tau to spread, some still unknown NANO virus or Bacteria?
February 6th, 2012 at 1:03 am
Interesting read but several questions still remain.
Such as, what is causing the Tau to spread, some still unknown NANO virus or Bacteria?
February 6th, 2012 at 1:04 am
Interesting read but several questions still remain.
Such as, what is causing the Tau to spread, some still unknown NANO virus or Bacteria?
February 6th, 2012 at 10:33 am
Peroxynitrites have been implicated in the hyperphosphorylation and nitration of tau proteins. Nitrated tau proteins misfold and apparently can spread to other parts of the brain. Peroxynitrite oxidation can lead to the misfolding of prions and of the superoxide dismutase which may also spread to other parts of the brain leading to more peorxynitrite formation. Alzheimer’s disease is not an infectious disease. In addition, peroxynitrite scavengers can likely be used to treat the disease.
February 6th, 2012 at 1:36 pm
There is a potential link between activity of some viruses to raise cytoplasmic Ca levels and in ability of tau itself to raise Ca. Add data the show elevated cyto Ca activates tau phosphoryation and dephosphorylation and we have the basis of a sustained propagating mechanism. The old olfactory nerve studies may have revealed a viral initiator that is no longer required once tau-Ca feedback becomes self-sustaining. Need hardly add that elevated Ca would enhance synaptic activity and elevate post-synaptic Ca.
Free radical mechanisms absolutely require their measurement in AD. Ischaemic heart research went through that craze in ’80s until measurement in ischeamic-rperfused heart failed to reveal levels of ROS needed to produce obseved injury.
February 6th, 2012 at 7:23 pm
Actually Alzheimer’s is an infectious disease, just not in the manner ordinarily meant. This study is showing that Alzheimer’s is infectious at the cellular level.
Although Alzheimer’s is not ordinarily infectious from individual to individual, it likely is under extraordinary circumstances. Person to person transmission has been demonstrated for Kuru. Inter-species transmission is known for Mad Cow. All these diseases are based upon prions and the transmission mechanism is consumption of an infected brain.
Finally, I am a Human brian. Ich bin ein Human brian!!
:-)