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Why Alzheimers Disease May Require a Broader Treatment Plan

Curated by Claudia Shannon / Research Scientist / ishonest

The World Health Organization (WHO) estimates that more than 55 million people worldwide live with Alzheimer’s disease or some related form of dementia. As individuals age, the prevalence of this disease doubles every 5 years past the age of 65 years. In fact, age is the most significant factor in developing Alzheimer’s.

Although diagnostic information to confirm the presence of Alzheimer’s is improving, no treatments have been effective in slowing its progression.

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“Despite decades of research, we still have no disease-modifying treatment and no cure,” said Genova.

A recent study that appears in the Journal of Molecular Neuroscience explains why understanding the neurodegeneration that occurs in Alzheimer’s disease — and thereby developing treatment options — is much more challenging than health experts previously thought.

Brain degeneration

Brain cells, or neurons, contain a specialized protein called tau, which is responsible for transporting nutrients and other substances from one part of the neuron to another. Researchers have identified tau dysfunction in several human brain neurodegenerative diseases.

Degeneration within the brain begins in one location and transmits from cell to cell, spreading across the brain and causing widespread damage and loss of brain tissue. Scientists believe that in the case of Alzheimer’s, the accumulation of the beta-amyloid 42 protein or injury to the brain can result in malformed tau.

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As the pathogenic tau spreads from cell to cell, it causes a web of neurofibrillary tangles to form. These tangles are a major hallmark leading to the neuronal death observable in Alzheimer’s disease.

Seemingly contradictory data have resulted from the past work toward Alzheimer’s therapeutics. Much of this research has approached the problem from the standpoint of cells taking up typical tau protein differently from how they take malformed tau.

This approach looks for an enzyme or protein specifically responsible for the uptake of malformed tau. If researchers can isolate this enzyme or protein, then a single therapeutic technique could turn off the uptake, much like turning off a light switch.

While this line of reasoning has been successful for certain other diseases, such as cystic fibrosis and diabetes, the evidence that Prof. Robinson’s team of researchers found challenges the current school of thought.

A broader treatment needed

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“They decided to work together on this, leading to the amazing result that even normal tau was taken up readily by cells from the brain.”

“[T]here are actually several pathways for tau to enter the cells. While pathogenic tau may be taken up slightly faster than normal tau, neurons and other cells in the brain take up both forms relatively quickly (in minutes),” Prof. Robinson explains.

“That means that keeping neurons passing healthy tau, rather than malformed tau, will take a much more nuanced treatment approach.”

So, the most effective treatment for people with Alzheimer’s may involve a mixture of drugs to address different elements of the disease.

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“Based on our findings, Alzheimer’s requires a similar approach to HIV treatment, where you have a cocktail of drugs used to address different elements of the disease. Together, these drugs work toward the larger goal: treating the symptoms of Alzheimer’s in a particular patient.”

– Prof. Robinson

Future research

While this new data give scientists a clearer picture of how Alzheimer’s forms and spreads within the brain, Prof. Robinson noted that further research regarding tau is necessary.

“The next step is to study tau uptake and cellular pathways in either brain slices from animal models or with tau isolated from different brain samples, such as healthy brain versus diseased brain,” said Prof. Robinson.

“We think that untangling the different pathways will be very important in understanding how to prevent further disease progression in Alzheimer’s and related diseases.”

Read more on: treatment, alzheimers


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