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Alzheimer'due south is a illness of protein assemblage. Amyloid-beta (Aβ) protein fibrils are terrible trivial fragments of protein that tangle upwards in Gordian knots, like earbud cords stuffed hastily in your pocket, and they build upward and form creeping, spreading structures in the brain called plaques. The stuff is like cerebral kudzu: When it gets out of control, it's lethally bad for its environment. It insinuates itself between the neurons of the hippocampus and neocortex and their support cells. It strangles out their ability to lay downward new memories or recall erstwhile ones. Now, a squad of researchers from Berkeley has discovered a connection between Aβ plaques and a protein chosen tau — and in the process, they used PET scanning to stage Alzheimer's disease in living people for the first fourth dimension.

Tau has a known function in neurons when it's behaving. It's part of the cytoskeleton, holding structural microtubules together like back up collars on collapsible tent poles. It supports the slender axonal transport conduit that maintains and nourishes the synapses at the distal ends of neurons. During the form of normal crumbling, the torso's normal housekeeping measures just get a little less good at sweeping the brain free of the debris and waste matter that accumulate backside the blood-brain bulwark. This is an expected consequence of aging, and in fact, "Tau is basically present in almost every aging encephalon," said Michael Schöll, ane of the atomic number 82 authors of the study. "Very few old people have no tau." Information technology tends to build upwardly in the medial temporal lobe, near the hippocampus.

In Alzheimer's disease, though, tau fibrils can get wrapped up in a runaway phosphorylation process. Information technology results in "neurofibrillary tangles," which can recruit normal tau proteins and clog up the whole works within a neuron, a lot like the fibrous mat of schmutz currently filling your PC instance fan. Eventually the aggregation destroys the neuron's internal send organisation, choking it to decease from the inside. For a brain afflicted with Alzheimer's, when the Aβ plaques showtime to show upward, the tangles evidence themselves, too. "Amyloid may somehow facilitate the spread of tau, or tau may initiate the deposition of amyloid. We don't know. We can't answer that at this point," said Dr. William Jagust, another atomic number 82 author. But when the buildup of tau can spread to other brain regions similar the neocortex, "that is when real problems begin," said Schöll. "We call up that may be the beginning of symptomatic Alzheimer's disease."

Tau protein buildup

Tau protein buildup. Prototype: Michael Schöll

Imaging the dysfunction

One of the biggest problems in Alzheimer's research is that y'all can't get a decisive diagnosis until the dissection — and that'south if in that location's even an dissection performed. The telltale amyloid plaques tin can't be seen until the brain can exist closely examined nether a microscope, and the progression of neurofibrillary tangles through brain tissue can be described by a process called Braak staging. Since biopsies on living brains are obviously to be avoided, this presents a major obstacle to accurate diagnosis and treatment, especially since early detection is obviously of import. But the Berkeley team found that PET scans can turn up evidence of tau assemblage in "people who are not only live, but who accept no signs of cognitive impairment," said Jagust. "This opens the door to the use of PET scans as a diagnostic and staging tool."

The team worked with 53 adults aged between xx and 77, subjects who had brain function falling forth a continuum from healthy normalcy to "likely Alzheimer's dementia." What the team saw on PET scans of those people ran in direct parallel to what Braak staging turns up postmortem. Nosotros still don't have a smoking gun. Just if there's a way to cure this disease, we'll get there via the ability to diagnose Alzheimer'southward conclusively before decease.

DOI: 10.1016/j.neuron.2016.01.028