JHU team demystifies 'one-two punch' that causes Alzheimer’s disease


In Alzheimer’s disease, the interaction between the buildup of tau proteins inside brain nerve cells and the accumulation of beta-amyloid outside these cells has been unclear. Using mouse models, Johns Hopkins scientists have shed light on this relationship, which could pave the way to more effective therapies.

Previous studies of early-onset Alzheimer’s have suggested the aggregation of beta-amyloid outside the cells is responsible for the clumping of tau proteins inside them, which causes brain cell degeneration and dementia. Instead, the new study shows that beta-amyloid buildup “is insufficient” to cause tau to “convert” from a normal state into an abnormal state in which it accumulates. Instead, it indirectly affects tau buildup by bringing about a “chain of chemical signaling events” that leads to its “conversion” into its clumping state.

“For the first time, we think we understand that the accumulation of amyloid plaque alone can damage the brain, but that’s actually not sufficient to drive the loss of nerve cells or behavioral and cognitive changes,” Wong said in a statement. “What appears to be needed is a second insult--the conversion of tau--as well.”

Whitepaper Download

Reducing the Complexity and Costs of Channel Planning and Logistics

How can you make the process of bringing your product to market less complex while also reducing costs? This Whitepaper identifies opportunities to simplify channel strategies for biopharma companies, their customers and patients. Discover how you can deliver savings and innovation to your business.

The team crossbred two groups of genetically modified mice to create a model that reflected more accurately the development of dementia in humans. The first group was engineered to accumulate beta-amyloid, while the second was engineered to accumulate tau protein in response to a tau fragment. They found in brain dissections that while beta-amyloid plaques weren’t able to directly “convert” tau to an abnormal state, their presence in the brain was still needed for tau to start clumping.

This could be why some drugs intended to treat Alzheimer’s after the “conversion” of tau have failed, Wong said in the statement. “If you were to intervene in the time period before the conversion of tau, you might have a good chance of ameliorating the deficits, brain cell loss and ensuing consequence of the disease,” he said. And the results also suggest that a combination therapy to combat the buildup of beta-amyloid and the clumping of tau could be successful.

- here's the statement

Related Articles:
Approved HIV drug could ward off Alzheimer’s disease
Rockefeller scientists start testing glutamate-clearing drug in Alzheimer’s patients
Transatlantic team reverses Alzheimer's, Parkinson's symptoms in fruit flies


Suggested Articles

The clinical testing giant LabCorp will now begin rolling out a blood test for lung cancer developed by Resolution Bioscience.

Silverback Therapeutics reeled in $85 million to advance its lead antibody-drug conjugate through the clinic and develop its earlier-stage pipeline.

Cognoa aims to equip pediatricians with an AI-powered app that can spot the signs of autism, allowing them to diagnose in the doctor's office.