The research, published in the journal Proceedings of the National Academy of Sciences,
provides clues as to why certain people develop Alzheimer's Disease
(AD) and it may be a step towards a diagnostic test that identifies
individuals at risk. The degenerative condition is the most common
cause of dementia and it affects around 417,000 people in the UK.
The APOE4 genetic variant is found in about a quarter of the
population. Not everyone who carries the variant will go on to develop
AD, but people who inherit one copy of APOE4 have up to four times the
normal risk of developing the late-onset variety of the disease. People
who have two copies have around ten times the normal risk.
The researchers behind today's study stress that most carriers of
APOE4 will not go on to develop Alzheimer's and carriers should not be
alarmed by the study's findings.
Differences in the region of the brain involved in memory, known as
the hippocampus, have previously been shown in middle-aged and elderly
healthy carriers of APOE4. However, the new Oxford University and
Imperial study is the first to show hyperactivity in the hippocampus of
healthy young carriers. It is also the first to show that APOE4
carriers' brains behave differently even at 'rest'.
The study used functional Magnetic Resonance Imaging (fMRI) carried
out at the University of Oxford to compare activity inside the brains
of 36 volunteers, with 18 carrying at least one copy of the APOE4 gene
and 18 non-carriers acting as controls.
All the volunteers in the study were aged between 20 and 35 and all
performed normally on tasks designed to test their cognitive skills.
The researchers looked at how the volunteers' brains behaved while
they were resting and also while they were performing a memory-related
task. Even when the APOE4 carriers were resting, the researchers could
see that carriers and non-carriers each had distinct patterns of brain
activity. The fMRI scans showed visible differences in how the
hippocampus was relating to the rest of the brain.
The researchers will now carry out a similar study of patients with
mild cognitive impairment to explore how these differences in patterns
of brain activity in young people may be associated with later changes.
Dr Clare Mackay, the lead author of the study from the Department of
Psychiatry and the Centre for Functional Magnetic Resonance Imaging of
the Brain at the University of Oxford, said: "We have shown that brain
activity is different in people with this version of the gene decades
before any memory problems might develop. We've also shown that this
form of fMRI, where people just lie in the scanner doing nothing, is
sensitive enough to pick up these changes. These are exciting first
steps towards a tantalising prospect: a simple test that will be able
to distinguish who will go on to develop Alzheimer's."
Dr Christian Beckmann, another author of today's study from the
Division of Neurosciences and Mental Health at Imperial College London,
added: "Our brains are always active - our minds wander even when we're
not carrying out specific tasks. We were surprised to see that even
when the volunteers carrying APOE4 weren't being asked to do anything,
you could see the memory part of the brain working harder than it was
in the other volunteers. Not all APOE4 carriers go on to develop
Alzheimer's, but it would make sense if in some people, the memory part
of the brain effectively becomes exhausted from overwork and this
contributes to the disease. This theory is supported by studies that
have found the opposite pattern in people who have developed
Alzheimer's, with these people showing less activity than normal in the
memory part of the brain."
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