Published on: March 27, 2015
by Rebekah Marcarelli for HNGN:
Researchers discovered Alzheimer’s disease is most likely driven by the progression of dysfunctional tau protein, and not amyloid as has been previously suggested.
The findings provide new insights into the roles played by amyloid and tau in the development of Alzheimer’s symptoms such as cognitive decline and memory loss, Mayo Clinic reported. The study results suggest stopping toxic tau could be a promising new focus in research on Alzheimer’s treatments.
“The majority of the Alzheimer’s research field has really focused on amyloid over the last 25 years,” said Melissa Murray, a neuroscientist at Mayo Clinic. “Initially, patients who were discovered to have mutations or changes in the amyloid gene were found to have severe Alzheimer’s pathology — particularly in increased levels of amyloid. Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer’s models were based on amyloid toxicity. In this way, the Alzheimer’s field became myopic.”
To make their findings, a team of researchers observed the evolution of amyloid and tau through different stages of Alzheimer’s progression using neuropathologic measures. They looked at 3,618 brains from Mayo Clinic’s postmortem brain bank, and 1,375 of them were confirmed to have had Alzheimer’s. The patients died at different ages and different stages of the Alzheimer’s progression. The team used a scoring system to evaluate the evolution amyloid and tau in the brains. The research revealed the severity of tau predicted the age onset and duration of the disease, but the same was not true for amyloid.
In a second part of the study, the researchers looked at amyloid brain scans taken of patients prior to death and compared the results to scans that measured tau and amyloid brain pathology. They found the signal from amyloid brain scans matched up with amyloid pathology observed in the vessels, but did not correspond with tau pathology. Some of the patients exhibited amyloid pathology that did not reach the threshold that would be expected in a scan of a brain affected by Alzheimer’s. The researchers also noted amyloid can be found in the brains of those who have not experienced cognitive decline.
“Tau can be compared to railroad ties that stabilize a train track that brain cells use to transport food, messages and other vital cargo throughout neurons,” Murray said. “In Alzheimer’s, changes in the tau protein cause the tracks to become unstable in neurons of the hippocampus, the center of memory. The abnormal tau builds up in neurons, which eventually leads to the death of these neurons. Evidence suggests that abnormal tau then spreads from cell to cell, disseminating pathological tau in the brain’s cortex.”
Amyloid begins to accumulate in the outer parts of the cortex first, and then spreads to the hippocampus and other areas of the brain. The observations showed a relationship between amyloid and cognitive decline, but once Tau was taken into account, the correlation was no longer relevant, suggesting tau is the primary driver of Alzheimer’s.
“Our findings highlight the need to focus on tau for therapeutics, but it also still indicates that the current method of amyloid brain scanning offers valid insights into tracking Alzheimer’s,” Murray said. “Although tau wins the ‘bad guy’ award from our study’s findings, it is also true that amyloid brain scanning can be used to ensure patients enrolling for clinical trials meet an amyloid threshold consistent with Alzheimer’s — in lieu of a marker for tau.”
The findings were published in a recent edition of the journal Brain.
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