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Alzheimer’s disease risk genes have early effects on the brain

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Alzheimer's disease

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The genetic predisposition to late-onset Alzheimer’s disease affects how the brain of young adults copes with specific memory tasks. Researchers at the Center for Neurodegenerative Diseases (DZNE) in Germany and Ruhr University Bochum report this in a scientific journal. Current biology.. Their findings are based on magnetic resonance imaging studies of individuals about the age of 20. Scientists suspect that the observed effects may be associated with the earliest disease processes.

The cause of Alzheimer’s disease in old age is not well understood. Is believed to be It is caused by an unfavorable interaction of lifestyle, external factors and genetic risks. The greatest genetic risk factor for late-onset Alzheimer’s disease comes from hereditary mutations that affect apolipoprotein E (ApoE), a protein associated with fat metabolism and neurons. Three variants of the ApoE gene are known. The most common form is associated with the average risk of Alzheimer’s disease. One of the two rare variants represents increased risk and the other represents reduced risk.

“I was interested in finding out if and how various genetic mutations affect brain function, so scanners must solve the challenge of young adults challenging their memory. I examined their brains while they weren’t, “Dr. Hweeling Lee explained. The person who led the current research at DZNE in Bonn.

Distinguish between similar events

The group of study participants consisted of 82 young men and women. They were on average 20 years old and were college students who were all considered cognitively healthy. On average, 33 of them had an increased risk of developing Alzheimer’s disease in the late stages and a decrease of 15 according to the ApoE genotype. During the study with the brain scanner, all individuals were presented with more than 150 consecutive images displayed on the monitor. These were everyday things such as hammers, pineapples and cats. Some photos were displayed repeatedly after a while, but the position of the objects displayed on the screen could change. Survey participants needed to see if the object was “new” or previously displayed, and if so, if its position had moved.

“We tested the ability to distinguish similar events from each other, which is called pattern separation,” Hweeling Lee said. “To For example, it’s important to remember if the key was placed in the drawer on the left or right side of the dresser, or where the car was parked in the parking lot. We easily simulated this situation by changing the position of the drawn objects. “

High resolution with the latest technology

At the same time as this experiment, volunteer brain activity was recorded using a technique called “functional magnetic resonance imaging.” The focus is on the hippocampus, which is an area only a few cubic centimeters in size, which is found only once in each hemisphere of the brain. The hippocampus is considered a memory switchboard. It also belongs to the section of the brain where the first damage occurs in Alzheimer’s disease.

When measuring brain activity, the scanner was able to show its full potential. It was an “ultra-high magnetic field tomography” with a magnetic field strength of 7 Tesla. Such devices can achieve better resolution than the brain scanners typically used in medical examinations. This allowed researchers to accurately record brain activity in various subfields of the hippocampus. “So far, participants with the ApoE genotype have not had such a detailed level of comparable study, which is a unique feature of our study,” said Hweeling Lee. I will.

There is no difference in memory performance

There was no difference between the three groups of subjects in terms of their ability to separate patterns. “In the memory test, all study participants performed equally well,” said Nikolai Axmacher, a professor of neuropsychology. “It doesn’t matter if the risk of Alzheimer’s disease increased, decreased, or averaged. It wasn’t. Such results can be expected of healthy young people. ” At Ruhr University’s Bochum, which also participated in the current survey. “However, .. Different groups of study participants activated different subfields of the hippocampus in different ways and to varying degrees. Therefore, their brains responded differently to memory tasks. In fact, there were differences in brain activation not only between the average and high-risk individuals, but also between the average and low-risk individuals. “

It is currently unclear whether these effects are important for the development of Alzheimer’s disease in old age. “Our findings may be related to very early disease processes. Determining this is a subject of future research and devising biomarkers for the early diagnosis of dementia. May help, “said Hweeling Lee. “In any case, Alzheimer’s disease is already reflected in In young adulthood. ”


People at high risk of Alzheimer’s disease have difficulty navigating


For more information:
Hweeling Lee et al, The risk of genetic Alzheimer’s disease affects the neural mechanism of pattern segregation in the hippocampal subfield, Current biology (2020). DOI: 10.1016 / j.cub.2020.08.042

Quote: Alzheimer’s disease risk genes have early effects on the brain (September 15, 2020).

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