Researchers have unveiled the structure of a unique amyloid beta protein associated with Alzheimer’s (AD) progression. This protein forms small aggregates that disrupt brain function. Importantly, the study found that lecanemab, a recently FDA-approved Alzheimer’s treatment, can neutralize these disruptive aggregates, hinting at its potential to slow down the disease’s cognitive decline.
Researchers have detailed the structure of a distinct type of amyloid beta plaque protein that plays a role in Alzheimer’s disease progression. These proteins form small, diffusible aggregates that can disrupt neuronal function across various regions of the brain. Lecanemab, an antibody therapy recently approved by the FDA for Alzheimer’s treatment, has been found to neutralize these small, diffusible amyloid beta protein aggregates. This suggests it may play a significant role in slowing cognitive decline in patients with early Alzheimer’s disease. The study also provided a clearer definition of the ‘protofibril’ or ‘oligomer’ structures that lecanemab binds to, potentially offering valuable insights into the drug’s mechanism of action against Alzheimer’s disease.

For the first time, researchers described the structure of a special type of amyloid beta plaque protein associated with Alzheimer’s disease (AD) progression.

In a report published May 10 in the journal Neuron, scientists showed the small aggregates of the amyloid beta protein could float through the brain tissue fluid, reaching many brain regions and disrupting local neuron functioning.  The research also provided evidence that a newly approved AD treatment could neutralize these small, diffusible aggregates. As a cause of dementia, AD affects more than 50 million people worldwide. Previous research has discovered that AD patients have abnormal build-up of a naturally occurring substance—amyloid beta protein—in the brain that can disrupt neurotransmission.

Currently, there is no cure for the disease. But in recent years, scientists have developed new treatments that can reduce AD symptoms such as memory loss.

Source: https://www.eurekalert.org/
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https://neurosciencenews.com/

The aging global population is the greatest challenge faced by 21st-century healthcare systems. Even COVID-19 is, in a sense, a disease of aging. The risk of death from the virus roughly doubles for every nine years of life, a pattern that is almost identical to a host of other illnesses. But why are old people vulnerable to so many different things?

It turns out that a major hallmark of the aging process in many mammals is inflammation. By that, I don’t mean intense local response we typically associate with an infected wound, but a low grade, grinding, inflammatory background noise that grows louder the longer we live. This “inflammaging” has been shown to contribute to the development of atherosclerosis (the buildup of fat in arteries), diabetes, high blood pressure , frailty, cancer and cognitive decline.

Now a new study published in Nature reveals that microglia — a type of white blood cells found in the brain — are extremely vulnerable to changes in the levels of a major inflammatory molecule called prostaglandin E2 (PGE2). The team found that exposure to this molecule badly affected the ability of microglia and related cells to generate energy and carry out normal cellular processes.

Fortunately, the researchers found that these effects occurred only because of PGE2’s interaction with one specific receptor on the microglia. By disrupting it, they were able to normalize cellular energy production and reduce brain inflammation. The result was improved cognition in aged mice. This offers hope that the cognitive impairment associated with growing older is a transient state we can potentially fix, rather than the inevitable consequence of aging of the brain. Levels of PGE2 increase as mammals age for a variety of reasons — one of which is probably the increasing number of cells in different tissues entering a state termed cellular senescence. This means they become dysfunctional and can cause damage to tissue by releasing PGE2 and other inflammatory molecules.

But the researchers also found that macrophages — another type of white blood cells related to microglia — from people over the age of 65 made significantly more PGE2 than those from young people. Intriguingly, exposing these white blood cells to PGE2 suppressed the ability of their mitochondria — the nearest thing a cell has to batteries — to function. This meant that the entire pattern of energy generation and cellular behavior was disrupted.

Although PGE2 exerts its effects on cells through a range of receptors, the team were able to narrow down the effect to interaction with just one type (the “EP2 receptor” on the macrophages). They showed this by treating white blood cells, grown in the lab, with drugs that either turned this receptor on or off. When the receptor was turned on, cells acted as if they had been exposed to PGE2. But when they were treated with the drugs that turned it off, they recovered. That’s all fine, but it was done in a petri dish. What would happen in an intact body?

The researchers took genetically modified animals in which the EP2 receptor had been removed and allowed them to grow old. They then tested their learning and memory by looking at their ability to navigate mazes (something of a cliche for researchers) and their behavior in an “object location test.” This test is a bit like someone secretly entering your house, swapping your ornaments around on the mantelpiece and then sneaking out again. The better the memory, the longer the subject will spend looking suspiciously at the new arrangement, wondering why it has changed.

It turned out that the old genetically modified mice learned and remembered just as well as their young counterparts. These effects could be duplicated in normal old mice by giving them one of the drugs that could turn the EP2 receptor off for one month. So it seems possible that inhibiting the interaction of PGE2 with this particular receptor may represent a new approach to treating late-life cognitive disorders.

Source: https://www.theconversation.com/

A new study found that a simple blood test can detect beta-amyloid protein buildup in a person’s brain years before Alzheimer’s disease symptoms appear. High amounts of beta-amyloid can clump together and form plaques on the brain, which is strongly associated with Alzheimer’s disease. Other research has found that amyloid plaques can appear as early as 20 years before the first sign of Alzheimer’s symptoms, such as cognitive decline and memory loss.

In the study, 158 adults in their 60s and 70s — most of whom had normal cognitive function — underwent a PET scan to spot amyloid plaque in the brain, and a blood test to measure beta-amyloid in the body. The blood test looked for two forms of beta-amyloid protein: beta-amyloid 42 and beta-amyloid 40. When beta-amyloid begins to build up, the ratio between the two proteins changes, and the blood test detects this.

The researchers labeled each blood test result as either amyloid positive or negative. They then compared them with the PET scans. They found that the PET scans confirmed the blood test results  88% of the time. When other risk factors were included, such as age and the appearance of the gene variant ApoE4 (which also is linked to a higher risk for Alzheimer’s), the test’s accuracy rose to 94%.

While there is some debate as to whether amyloid plaque actually causes Alzheimer’s, a simple blood test that indicates you may be at a higher risk of the disease would be one more reason to adopt lifestyle changes. The researchers added that they expect the blood test to be available within a few years.

The results were published online Aug. 1, 2019, by the journal Neurology.

Source: https://www.health.harvard.edu/

Unfortunately, we can’t go hard forever. But in the future, that might not be a problem: New research has revealed how to harness the cognitive benefits of a workout — without the actual workout. Scientists think this help slow aging in the brain. A study published Thursday in Science suggests the benefits of exercise run in the blood and may be able to be transferred from one swoll organism to another, less-swoll one.