Newer Discoveries in Alzheimer’s Disease Research
Alzheimer’s Disease (AD) is an increasingly prevalent topic in elder health care and studies, often with new information and research seen in news headlines weekly or monthly. Assisted Living Education covers some of these new discoveries in the latest research movements for Alzheimer’s treatments.
A good portion of these research and technologies are still in the early stages, and often haven’t gone beyond laboratory testing on mice. Much of this recent research has been conducted on mice engineered to display similar neuropathology as seen in a human individual with Alzheimer’s. However, with these encouraging new discoveries, researchers are hoping to eventually replicate the successful results in humans as well.
Beta-Amyloid & Tau Tangles
Beta-amyloid plaques and tau protein tangles have been the target of heavy AD research for the last two to three decades. Analysis has indicated that people with AD have an increased amount of beta-amyloid plaques and tau, or neurofibrillary, tangles in their brain.
In a healthy brain, the cell transport system is arranged in what look microscopically like parallel lines, called microtubules. Nutrients and other materials flow along these lines, and normal tau proteins provide the structural support to keep these lines and order in tact. Sometimes, these tau proteins become corrupted, causing structural collapse and twisting. As a result, the transport system is disrupted and eventually leads to cell death. Tau pathologies have also been linked with other degenerative brain conditions, including frontotemporal lobe dementia, progressive supranuclear palsy, and chronic traumatic encephalopathy.
Previously, it was thought that beta-amyloid itself led to the development and acceleration of Alzheimer’s Disease. Interestingly, studies have revealed that not only are the tau tangles more indicative of Alzheimer’s destruction, but that the beta-amyloid is the one contributing to the corruption of the tau proteins, thus leading to the tau tangles.
Much of the current medical research has focused on either inhibiting the production or the clustering of these plaques by employing the body’s immune system against them. Researchers are experimenting with drugs called monoclonal antibodies, which mimic the body’s natural antibodies that act against foreign invaders. These can help prevent the clumping and assist the body in flushing the beta-amyloid from the brain. Tau aggregation inhibitors as well as other tau treatments are under current research as well.
Ultrasound technologies are a novel approach that focuses on breaking up the plaques and tangles developed from beta-amyloid and tau proteins. A team in Queensland, Australia, led by Gerhard Leinenga and Jürgen Götz, developed what they call focused therapeutic ultrasound, which concentrates sound waves into brain tissue. The oscillations of the sound waves encourage the relaxation of the blood-brain barrier, and stimulate microglial cells to activate. Microglial cells are responsible for waste removal from the brain, and with their activation, they can clear out the beta-amyloid plaques.
To replicate ‘Alzheimer’s’ in the lab, researchers deposit beta-amyloid in the brains of mice. 75% of the mice tested experienced a full recovery in memory function and improved task performance from the ultrasound treatment. Better yet, this procedure is non-invasive with no damage to the surrounding brain tissue.
HSV-1 & Alzheimer’s
Some research has examined which, if any, environmental factors have played a part in the development of AD. A case has been made for the involvement of the HSV-1 (Herpes Simplex Virus 1), as a correlation between persistent brain infections caused by the virus has been noted.
HSV-1’s interaction with the body’s proteins during an active infection are thought to have a cumulative effect, especially with recurrent flare-ups. The virus interferes with the host’s cell processes, helping itself replicate and interfere with the proteins related to immune response. The host may even cause damage to itself in an attempt to combat the virus with increased inflammatory and immune responses, leading to a few different outcomes. In severe cases, affected individuals may develop herpes simplex encephalitis (HSE), but cell death and neurodegeneration are other effects that may initially go unnoticed.
In this approach, future AD treatments could involve the use of antiviral agents already used in targeting HSV-1, but interestingly, the use of statins as well. Statins help lower cholesterol, and it appears that they also have a role in regulating pathogen entry. This could help reduce the spread of HSV-1 throughout the body and brain.
Lack of Deep Sleep
There has been a long-time correlation between sleep disorders and those who suffer from AD, but common thought surmised that the brain’s sleep regulators were suffering from the effects of AD. Research is taking a new turn, suggesting that the lack of deep sleep is in fact contributing to the development of AD.
Healthy sleep enables restorative measures in the human body, purging toxins and repairing other body systems. However, the inability to acquire or reach deep sleep can lead to a build-up of these toxins, including beta-amyloid in the brain. While the body relies on the lymphatic system to help clear out its toxins and waste, the brain relies on the glymphatic system, named for the microglial cells responsible for toxin and waste removal specific to the organ.
General sleep disorders and those specific to Alzheimer’s research have undergone human trials, finding that lack of sleep causes poor memory and accumulation of beta-amyloid. A study by Mander, Jagust, and Walker discovered that powerful brain waves generated during non-REM sleep help solidify memories from their short-term state in the hippocampus to their long-term existence in the frontal cortex.
The positive side for these findings is that treatments for poor sleep are relatively easier to access. One aspect is as simple as exercising more, but behavioral therapy and even electrical stimulation have been found to improve sleep and memory performance as well.
Aberrant Immune Response
Much of the treatments that we have just discussed revolve around the idea that the accumulation of beta-amyloid plaques and tau protein tangles are the primary causes for symptoms in AD.
However, some of the newer research has taken a different approach. In light of questioning why over 99% of clinical trials for AD treatments have failed, some researchers suggest that the treatments have gone after the wrong targets. They suggest that an aberrant immune response is actually destroying the neural synapses – the crucial connections that pass messages among the neurons.
L-Arginine & Immune Suppression
Basically, L-Arginine (or, arginine) is an amino acid essential for normal immune system function. In the past, some of the research has suggested that AD and other dementia disorders are a result of the body amping up its immune or inflammatory response. However, some research indicates that the immune response is actually suppressed, but in localized regions of the brain. In areas with accumulated beta-amyloid, there is an increase of arginase, an enzyme that catabolizes arginine, leading to an overall decrease of the amino acid in the brain. This also indicates that the neurons are suffering from nutrient deprivation from this excessive catabolization of arginine.
Arginine is found naturally in the human body, but is also present in our foods (meats, dairy, coconut, oats, walnuts, soybeans, peanuts, etc.). Though it would seem that increasing arginine in the diet would help counteract these negative effects, researchers are careful to warn that arginine supplementation will do little help in the case of AD. Though arginine levels may increase within the body, the blood-brain barrier has its limitations on how much it will allow to pass through. Instead, research has focused on inhibiting the arginase to prevent it from catabolizing arginine.
Synaptic Pruning & C1q Protein
Synaptic pruning is the process in which synapses that are either infrequently used or less efficient are marked for elimination. This is a normal and essential process in development, helping with brain function and efficiency.
However, like many things, this process can go awry. In this case, beta-amyloid and a protein called C1q seem to work together. C1q is another key component in immune response, the first in a chain reaction called a complement cascade. C1q binds to particular pathogens or other toxic cells/debris, ‘marking’ them for destruction. The other components in the complement cascade help advance the breakdown and elimination of these elements. The microglia are the immune cells specific to the brain that eliminate (ingest) cells or debris marked for destruction.
In individuals with AD, an excess of C1q was discovered especially at the synapses, amidst beta-amyloid plaques. According to Stanford Medicine, the levels of C1q were 300 times the average amount. It appears that overzealous C1q would mark too many synapses for destruction, while the beta-amyloid would stimulate the microglia to devour or engulf the synapse.
Researchers have found in the lab mice that inhibiting the C1q protein actually did stop this process. While their results have been successful with lab mice, they have a long way to go before seeing the human trials for this theory. Even so, it continues to open up new avenues in research involving the brain’s immune response and its effects on neurodegenerative disorders.
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