Risk gene for Alzheimer's has early effects on the brain

Date:
September 15, 2020
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
A genetic predisposition to late-onset Alzheimer's disease
affects how the brains of young adults cope with certain memory
tasks. Researchers find are based on studies with magnetic resonance
imaging in individuals at the age of about 20 years. The scientists
suspect that the observed effects could be related to very early
disease processes.



FULL STORY ==========================================================================
A genetic predisposition to late-onset Alzheimer's disease affects how
the brains of young adults cope with certain memory tasks. Researchers
from the German Center for Neurodegenerative Diseases (DZNE) and the Ruhr-Universita"t Bochum report on this in the scientific journal
Current Biology. Their findings are based on studies with magnetic
resonance imaging in individuals at the age of about 20 years. The
scientists suspect that the observed effects could be related to very
early disease processes.


==========================================================================
The causes for Alzheimer's in old age are only poorly understood. It
is believed that the disease is caused by an unfavorable interaction
of lifestyle, external factors and genetic risks. The greatest genetic
risk factor for late- onset Alzheimer's disease stems from inherited
mutations affecting "Apolipoprotein E" (ApoE), a protein relevant for
fat metabolism and neurons.

Three variants of the ApoE gene are known. The most common form is
associated with an average risk for Alzheimer's. One of the two rarer
variants stands for an increased risk, and the other for a reduced risk.

"We were interested in finding out whether and how the different gene
variants affect brain function. That is why we examined the brains of
young adults in the scanner while they had to solve a task that challenged their memory," explained Dr. Hweeling Lee, who led the current study at
the DZNE in Bonn.

Distinguishing similar events The group of study participants comprised of
82 young men and women. They were on average 20 years old, and all of them
were university students considered to be cognitively healthy. According
to their genotype for ApoE, 33 of them had an average, 34 an increased and
15 a reduced risk of developing Alzheimer's disease at a late age. During
the study in the brain scanner, all individuals were presented with more
than 150 successive images displayed on a monitor.

These were everyday objects such as a hammer, a pineapple or a cat. Some pictures were repeated after a while, but sometimes the position of
the displayed objects on the screen had changed. The study participants
had to identify whether an object was "new" or had been shown before --
and if so, whether its position had shifted.

"We tested the ability to distinguish similar events from one
another. This is called pattern separation," said Hweeling Lee. "In
everyday life, for example, it's a matter of remembering whether a key
has been placed in the left or right drawer of a dresser, or where the
car was parked in a parking garage. We simulated such situations in
a simplified way by changing the position of the depicted objects." High-resolution through modern technology Simultaneously to this
experiment, the brain activity of the volunteers was recorded using a
technique called "functional magnetic resonance imaging." Focus was on
the hippocampus, an area only a few cubic centimeters in size, which can
be found once in each brain hemisphere. The hippocampus is considered
the switchboard of memory. It also belongs to those sections of the
brain in which first damages occur in Alzheimer's disease.

When measuring brain activity, the scanner was able to show its full
potential: It was an "ultra-high field tomograph" with a magnetic field strength of seven Tesla. Such devices can achieve a better resolution
than brain scanners usually used in medical examinations. This enabled
the researchers to record brain activity in various sub-fields of the hippocampus with high precision. "Up to now, there were no comparable
studies with such level of detail in ApoE genotyped participants. This
is a unique feature of our research," said Hweeling Lee.

No differences in memory performance There were no differences between
the three groups of subjects with regard to their ability for pattern separation. "All study participants performed similarly well in the
memory test. It did not matter whether they had an increased, reduced or average risk for Alzheimer's disease. Such results are certainly to be
expected in young healthy people," said Nikolai Axmacher, Professor of Neuropsychology at the Ruhr-Universita"t Bochum, who was also involved in
the current study. "However, there were differences in brain activity. The different groups of study participants activated the various subfields
of the hippocampus in different ways and to varying degrees. Their brains
thus reacted differently to the memory task. In fact, we saw differences
in brain activation not only between people with average and increased
risk, but also between individuals with average and reduced risk."
At present, it is uncertain whether these effects are significant for developing Alzheimer's in old age. "Our findings might be related to very
early disease processes. Determining this is a task for future studies
and could help to devise biomarkers for the early diagnosis of dementia,"
said Hweeling Lee.

"In any case, it is remarkable that a genetic predisposition for
Alzheimer's disease is already reflected in the brain at young adulthood."

========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Hweeling Lee, Ru"diger Stirnberg, Sichu Wu, Xin Wang, Tony Sto"cker,
Sonja Jung, Christian Montag, Nikolai Axmacher. Genetic Alzheimer's
Disease Risk Affects the Neural Mechanisms of Pattern Separation
in Hippocampal Subfields. Current Biology, 2020; DOI: 10.1016/
j.cub.2020.08.042 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915110001.htm

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