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The Current State of Alzheimer’s Research: An Elusive Cure

Alzheimer’s research scientists around the world are working hard to discover new drugs and other treatments that could cure Alzheimer’s disease. But although the search has proved challenging so far, a cure seems a little less elusive now than it has been before. In this article, we’ll look at the current state of research for an Alzheimer’s disease cure and show you what the most promising research projects and clinical trials are focusing on.

An Elusive Cure in Alzheimer’s Research

Producing a new drug is a quest that can take 12 years or more and usually involves long-term, large-scale clinical trials. This is true for all diseases, and especially for a disease as complex as Alzheimer’s, whose fundamental cause still eludes scientists.

We’ve been knowing for decades that people with Alzheimer’s have plaques and tangles in their brains, which become progressively more pronounced as the disease progresses. Alzheimer’s researchers have also identified the proteins and enzymes responsible for their formation. But whether plaques and tangles in the brain cause Alzheimer’s or are only a consequence of other neurochemical process is up for debate.

An Alzheimer’s disease cure has been in sight for years now, but many promising studies and clinical trials have proved inconclusive—or outright failures. Early-stage studies don’t always show consistent results in trials, which creates challenges for researchers and make pharmaceutical companies careful with their millions.

Over the last few decades, huge sums have been poured into promising Alzheimer’s disease studies. Backed by billions in funding from governments and major organizations and equipped with state-of-the-art technology, researchers have powerful resources that they are trying to convert into the first Alzheimer’s cure. The stakes are high—dementia is predicted to double to 3.3% of the population by 2060, and Alzheimer’s will likely represent most of these cases.

The current drugs that treat the symptoms of Alzheimer’s disease do not address the disease’s underlying causes. Researchers are therefore trying to develop new drugs or adapt drugs that are being used to treat other conditions. Let’s take a closer look at the specific ways that researchers are trying to cure Alzheimer’s or modify its course.

An Old Culprit: The Beta-Amyloid Protein

The brains of people living with Alzheimer’s disease have abnormal levels of the beta-amyloid protein, which forms the plaques commonly associated with the disease. We’ve known this for years. These plaques interfere with brain cell communication and may disrupt the storage of new information.

Researchers have a good understanding of how abnormal beta-amyloid fragments form in the brain from the parent amyloid precursor protein through the interference of the enzymes beta-secretase and gamma-secretase. Disrupting this process could prevent the formation of plaques.

The beta-amyloid hypothesis is an old one and a lot of effort has been invested over the last decades into studies that aimed to block this protein one way or another. However, all of them failed. But researchers today have a better understanding of the underlying processes involving the creation of beta-amyloid than before—and the insights that came from previous failures.

Ongoing clinical trials are testing drugs that act in novel ways to try to prevent beta-amyloid from forming plaques or to clear it from the brain. Other studies look for an effective strategy to block the activity of beta-secretase.

Two studies known as the Alzheimer’s Prevention Initiatives are trying to determine whether anti-amyloid compounds are effective in combating plaque. The studies will be running until 2025.

A Vaccine Against Alzheimer’s?

Another feature of Alzheimer’s disease that researchers have observed in the brains of those who have died from the condition are neuronal tangles consisting chiefly of Tau protein. In a healthy brain, this protein maintains the structure of functioning neurons.

But in a brain affected by Alzheimer’s, unbalanced levels of the Tau protein could drive the progression of the disease. A vaccine that generates antibodies against the Tau protein has shown promising results in 2019 and continues to be studied in the hope that it will be soon tested on humans. If it proves effective, it could slow Alzheimer’s.

Brain Inflammation and Alzheimer’s Disease

Another ongoing study is testing the efficiency of Leukine, a drug that stimulates the body’s immune system. Inflammation could play an important role in the development of Alzheimer’s disease, as both Tau and beta-amyloid proteins trigger an immune response that produces toxic compounds in the brain.

The link between brain inflammation and Alzheimer’s is a newer lead for scientists. Drugs that target brain inflammation and its underlying processes could prove more effective than previous attempts to prevent the formation of plaques by targeting the beta-amyloid protein. The second phase of the Leukine study could be completed as soon as mid-2020.

The Link Between Cardiovascular Health and Alzheimer’s Disease

A growing body of evidence points to cardiovascular health as the key to brain health. Conditions that damage the heart or arteries seem to increase the risk of Alzheimer’s disease. The main culprits are heart disease, high blood pressure, high cholesterol, diabetes, and stroke.

Researchers are now looking beyond beta-amyloid and Tau protein blockers at blood pressure medication and other drugs that may help treat Alzheimer’s disease. At this point, however, it’s not yet clear how big an impact these drugs would have on someone already suffering from Alzheimer’s. Cardiovascular health could be just one of the factors impacting the development and progression of Alzheimer’s disease.

Preventing Senescence

Senescence refers to the process by which brain cells stop growing and dividing. Senescent cells cause the loss of neurons, affecting memory and one’s ability to acquire new information. These harmful cells linger in the brain, where they continue to secrete inflammation-triggering molecules.

Senolytic drugs can destroy these cells, offering the promise of a new way to tackle Alzheimer’s disease. They may reduce inflammation in the brain and prevent the formation of tangles resulting from the build-up of Tau protein. Some senolytic drugs are being used to treat other conditions, but in the future, we may see more specific applications of these to Alzheimer’s disease. A proof of concept study is underway.

Improving Communication Between Neurons

Other studies focus on specific receptors in the brain that reduce the number of neurotransmitters. Neurotransmitters are essential for effective communication between neurons, and people with Alzheimer’s have low levels of acetylcholine, one of the key neurotransmitters.

Pimavanserin, a drug that has proved effective in treating patients with Parkinson’s, blocks specific brain receptors that may play a role in Alzheimer’s disease. More specifically, it can reduce the effects of the psychotic symptoms that people with Alzheimer’s experience, and which is one of the disease’s most debilitating symptoms. At the time of writing, Primavanserin is pending FDA approval.

Could the Best Cure Be Prevention?

Alzheimer’s research also aims to prevent the disease in individuals who are more at risk of developing it, whether it’s because they have high levels of beta-amyloid in the brain or else carry specific genes associated with rare forms of the condition.

Even if the processes of reversing Alzheimer’s disease will continue to pose a great challenge for researchers, the possibility of a drug that can prevent the development of the condition at least in some specific groups could represent a major milestone in the fight against Alzheimer’s. It could yield key insights that could help with the development of increasingly effective treatments and, one day, a cure.

Examples of these studies include the DIAN-TU study, the Anti-Amyloid Treatment for asymptomatic patients, and the Alzheimer’s Prevention Initiative, all of which should be completed by 2022.

Final Thoughts on Alzheimer’s Research

The quest for an Alzheimer’s disease cure continues at a steady pace. Given the intricacies of the brain structures in focus and the complex nature of the disease, developing an Alzheimer’s cure remains a major challenge.

However, by continuing to explore potential treatments with different targets, as opposed to focusing exclusively on beta-amyloid proteins, researchers stand a better chance to find effective treatments for Alzheimer’s. As the Alzheimer’s Association claims on their website, “The first survivor of Alzheimer’s is out there.”