Tau, rather than amyloid, may cause Alzheimer’s disease

Kim Yun-mi  Published 2020.01.06  14:13  Updated 2020.01.06 14:13


After a recent study suggested that researchers advocating the “amyloid hypothesis” -- that the accumulation of amyloid-beta is the primary cause of Alzheimer's disease – could be wrong, a protein called tau is gaining attention as the more likely cause of the illness.

On Monday last week, the online issue of Neurology, a journal published by the American Academy of Neurology, released the study, which reversed the prevailing hypothesis on amyloid-beta.

The research found that a change in cognitive function preceded the formulation of amyloid-beta, concluding that amyloid-beta was not the primary cause of Alzheimer’s.

The research team, led by Dr. Kelsey R. Thomas of the VA San Diego Healthcare System, conducted the study on 747 people with an average age of 72 for four years.

The researchers divided the participants into three groups based on memory and thinking scores – 305 people with normal thinking and memory skills, 153 with subtle thinking and memory differences, and 289 with mild cognitive impairment. The participants received brain scans at the start of the study and had their amyloid-beta plaques checked once a year.

The results showed that the subtle thinking and memory differences group had a faster accumulation of amyloid compared to those with normal thinking and memory skills. The subtle differences group also had a more rapid thinning of the entorhinal cortex, a brain region affected early by Alzheimer’s disease.

In contrast, the researchers also found that people with mild cognitive impairment had more amyloid at the start of the study. Still, their amyloid accumulation was not faster than that of those with normal thinking and memory skills. However, they had not only brain shrinkage of the hippocampus but faster thinning of the entorhinal cortex.

The study also evaluated a protein called tau, another presumable biomarker for Alzheimer’s, and found that tangles of tau were consistent with the degree of cognitive decline.

The researchers concluded that plaques of amyloid beta were not the culprit of dementia, and the target of Alzheimer’s drug should be changed.

The research team added that more research was needed to check if tau is already present in the brain when subtle thinking and memory differences begin to appear.

Researchers have developed numerous candidate drugs to target amyloid based on the amyloid hypothesis, but no treatment obtained approval due to clinical failures.

Most recently, Biogen unveiled new results of studies on aducanumab, claiming that “additional data analysis showed that the investigational drug was effective on a high dose.” The company said it would seek the U.S. Food and Drug Administration’s approval but did not disclose a detailed timeline.

The pharmaceutical industry is switching its attention to tau from amyloid.

Candidates for anti-tau antibodies are Lilly’s zagotenemab, Biogen’s gosuranemab, Roche’s semorinemab, and AbbVie’s tilavonemab.

The four candidates are in phase-2 trials, and the results are expected to come this year and next year. Gosuranemab and tilavonemab have already experienced clinical failures, but Biogen and AbbVie are continuing studies on them as Alzheimer’s treatments.

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