Alzheimer’s patients suffer from various changes in their brains, but the exact cause of the disease is unknown
Science Photo Library/Alamy
New understanding of Alzheimer’s disease suggests that its root cause lies in the buildup of fat droplets in brain cells.
says targeting these droplets could lead to more effective treatments than current drug strategies targeting proteins Michael Haney at the University of Pennsylvania. “This opens up a new avenue for treatment development,” he said.
The most common explanation for Alzheimer’s disease is that it is caused by the buildup of a protein called beta-amyloid in plaques between nerve cells. Another suspect is the buildup of tangles made of another protein called tau stored inside nerve cells.
Debate over which of the two proteins is the culprit has raged for decades. The amyloid hypothesis is currently leading the charge, as some antibody therapies that eliminate amyloid in the brain have recently shown some effectiveness in slowing memory loss in Alzheimer’s patients.
But Haney said the debate ignores the fact that fat droplets can also be seen in the brains of people who die from the disease. German physician Alois Alzheimer first described these phenomena in the early 20th century, when he noticed the presence of amyloid plaques, tau tangles, and tau proteins in the brains of Alzheimer’s patients. fat droplets, giving the disease its name. But for decades, fat was mostly ignored.
In his latest study, Haney is investigating the biggest genetic risk factor for Alzheimer’s disease: a drug called APOE. It codes for proteins that help move fat in and out of cells.
People have different variants of this gene, called apolipoprotein2, 3 and 4. These, apolipoprotein2 The risk of developing Alzheimer’s disease is minimal, while apolipoprotein4 brought the most – although it wasn’t clear why until now.
To gain more insights, Haney and his colleagues conducted a series of experiments while he was at Stanford University in California. First, the team used a relatively new technology called single-cell RNA sequencing to identify which proteins are being produced in individual cells.They applied it to tissue samples from people who died of Alzheimer’s disease and had two copies apolipoprotein4 a variant or two copies of Apolipoprotein OE3.
This shows that the main difference between people with this disease apolipoprotein4 It’s that the immune cells in their brains have higher levels of a certain enzyme that works by increasing fat droplets in those cells.
In further experiments, the team grew these brain immune cells, called microglia, in a dish using cells from living people with any of the following diseases: apolipoprotein4 or Apolipoprotein OE3 Variants.Applying amyloid to cells causes them to accumulate fat, especially if they have apolipoprotein4 Variants.
The team concluded that in Alzheimer’s disease, amyloid accumulation triggers fat accumulation. This leads to a buildup of tau protein within neurons, which leads to cell death, leading to symptoms of memory loss and confusion.
Previous research has found that other genes also increase Alzheimer’s risk, but to a lesser extent apolipoprotein4tend to participate fat metabolism or immune systemwhich further supports their hypothesis, Haney said.
Ilondica Dias Researchers at Aston University in Birmingham, UK, who were not involved in the work, said previous studies have suggested that fat metabolism in other brain cells may also play a role. “The common thread that links all these (findings) is the involvement of lipid (fat) metabolism,” she said. “But it’s a very interesting paper.”
This finding comes despite separate studies showing harm APOE More than three-quarters of Alzheimer’s disease cases are caused by genetic mutations.That work, by Dylan Williams The study by University College London and colleagues is based on a population-based study called the UK Biobank, which documented APOE People with mutations have and track their health records.
Compared with people with two copies of the least risky variant, apolipoprotein2Those who carried one or two copies of the other variants were nearly four times more likely to develop Alzheimer’s disease, they reported in a report. Paper published online.
Williams said this means that if we could somehow interfere with this molecular pathway, about 75 percent of people with Alzheimer’s disease would not develop the disease. “Given that we are in a rare situation where differences in this protein appear to be responsible for much of the disease burden, if we could design drugs that could somehow mitigate this risk, we would hopefully prevent most of the disease.”
Blissfulcalmways
