Tau Pathology is the Main Cause of Alzheimer’s Disease

Tau tangles
Tau tangles
Researchers concluded that dysfunctional tau protein, not amyloid, is the main culprit behind Alzheimer's disease.

The progression of dysfunctional tau protein is the ultimate driver behind the cognitive decline and memory loss associated with Alzheimer’s disease.

The conclusion was reached after researchers from the Mayo Clinic examined more than 3,600 brains postmortem, concluding that the build-up of amyloid aids in dementia progression, but is not a primary cause of the neurodegenerative disease.

Findings from the two-part study, which were published in Brain, suggest that stopping the spread of toxic tau protein should be a new focus in Alzheimer’s research and drug development.

Researchers from the Mayo Clinic Florida location examined 3,618 postmortem brains, of which 1,375 were sourced from patients with a confirmed Alzheimer’s diagnosis. The patients were different ages and at different stages of dementia at death, which allowed researchers to observe a timeline of disease progression. Using a scoring system to evaluate amyloid and tau evolution in brain tissue, they found that the severity of tau, not amyloid, predicted the age of onset of cognitive decline, disease duration, and mental deterioration.

Afterwards, researchers at Mayo Clinic Rochester examined amyloid brain scans taken of patients prior to death and compared those scans to measures of tau and amyloid brain pathology. Although the signal from amyloid brain scans corresponded to amyloid pathology in the brain and not amyloid found in vessels, it did not correspond with tau pathology. As was expected, some brains had amyloid at pathology but not at the level observed in Alzheimer’s brain scans, since amyloid may develop in the brains of older people without manifesting as cognitive decline.

“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,” said study author Melissa Murray, PhD, in a press release. “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.”

Although amyloid has been the focus of Alzheimer’s research for at least the last 25 years, the findings indicate that amyloid progression may be just a progressive consequence of Alzheimer’s, while the far more toxic nature of tau pathology appears to be the driver behind the devastating disease.  


  1. Murray ME et al. Brain. 2015; doi:10.1093/brain/awv050.