Discovery reveals why toxic Alzheimer’s plaques don’t always lead to dementia


One of the fundamental pathological markers seen in patients suffering from Alzheimer’s disease is a build-up of two proteins – amyloid beta and tau – in the brain. It’s this action that many researchers hypothesize is the key symptomatic cause of cognitive decline associated with the disease. However, not all people with a build-up of these proteins display neurological damage and cognitive decline. New research from the University of Texas Medical Branch at Galveston may have finally homed in on the reason behind this strange observation, and the results could lead to a whole new way to battle this devastating disease.

Alzheimer’s research over the last few years has been both in flux and undergoing a renaissance. On the heels of several high-profile clinical trial failures, several major pharmaceutical companies started pulling back investment into new therapies. Questions were raised over the accuracy of the over-riding amyloid beta hypothesis, with some scientists suggesting research was centered on the wrong pathological targets. Alongside these doubts, a number of striking innovative discoveries opened up a variety of new potential treatment pathways.

This new research intriguingly offers a possible answer to the question of why amyloid beta build-up may not necessarily result in Alzheimer’s disease in all patients. An earlier study from the same team first demonstrated that for some people, these toxic protein accumulations tended to not specifically congregate at synapse points in the brain. This meant that these patients were essentially displaying similar neuropathology to those with Alzheimer’s, but with none of the cognitive decline.

“When nerve cells can’t communicate because of the buildup of these toxic proteins that disrupt synapse, thought and memory become impaired,” explains Giulio Taglialatela, corresponding author on the new study. “The next key question was then what makes the synapse of these resilient individuals capable of rejecting the dysfunctional binding of amyloid beta and tau?”

The team set out to examine a volume of frozen brain tissue from deceased subjects that had previously participated in brain aging studies. Synaptic protein composition was then analyzed in the brain tissue using a variety of techniques and the results were excitingly revealing. Those subjects with Alzheimer’s neuropathology, but no symptoms of dementia, were found to have a unique synaptic protein signature that was notably different from both Alzheimer’s patients with dementia and healthy control subjects with no visible Alzheimer’s-like neuropathology.

This unique signature comprises 15 specifically identified proteins that the researchers are hypothesizing confers a possible synaptic resistance to the neural damage both amyloid beta and tau can cause.

“We don’t yet fully understand the exact mechanism(s) responsible for this protection,” says Taglialatela. “Understanding such protective biological processes could reveal new targets for developing effective Alzheimer’s treatments.”

As Taglialatela is clear to say, no clear mechanism explaining how this combination of proteins results in a synaptic resistance to amyloid and tau accumulations has been uncovered, but the early research could have compelling implications for many in the Alzheimer’s research field. If this protective biological process can be understood and exploited it could prove to be an incredibly effective way to battle the degenerative symptoms of the disease.


The research was published in the Journal of Alzheimer’s Disease.

Source: University of Texas Medical Branch at Galveston

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