TORONTO, Dec. 3, 2013 /CNW/ - People who carry a high-risk gene for
Alzheimer's disease show changes in their brains beginning in
childhood, decades before the illness appears, new research from the
Centre for Addiction and Mental Health (CAMH) suggests.
The gene, called SORL1, is one of a number of genes linked to an
increased risk of late-onset Alzheimer's disease, the most common form
of the illness. SORL1 carries the gene code for the sortilin-like
receptor, which is involved in recycling some molecules in the brain
before they develop into beta-amyloid a toxic Alzheimer protein. SORL1
is also involved in lipid metabolism, putting it at the heart of the
vascular risk pathway for Alzheimer's disease as well.
"We need to understand where, when and how these Alzheimer's risk genes
affect the brain, by studying the biological pathways through which
they work," says Dr. Aristotle Voineskos, head of the Kimel Family
Translational Imaging-Genetics Laboratory at CAMH, who led the study.
"Through this knowledge, we can begin to design interventions at the
right time, for the right people." The study was recently published
online in Molecular Psychiatry with Dr. Voineskos's graduate student,
Daniel Felsky as first author, and was a collaborative effort with the
Zucker Hillside Hospital/Feinstein Institute in New York and the Rush
Alzheimer's Disease Center in Chicago.
To understand SORL1's effects across the lifespan, the researchers
studied individuals both with and without Alzheimer's disease. Their
approach was to identify genetic differences in SORL1, and see if there
was a link to Alzheimer's-related changes in the brain, using imaging
as well as post-mortem tissue analysis.
In each approach, a link was confirmed.
In the first group of healthy individuals, aged eight to 86, researchers
used a brain imaging technique called diffusion tensor imaging (DTI).
Even among the youngest participants in the study, those with a
specific copy of SORL1 showed a reduction in white matter connections
in the brain important for memory performance and executive function.
The second sample included post-mortem brain tissue from 189 individuals
less than a year old to 92 years, without Alzheimer's disease. Among
those with that same copy of the SORL1 gene, the brain tissue showed a
disruption in the process by which the gene translated its code to
become the sortilin-like receptor.
Finally, the third set of post-mortem brains came from 710 individuals,
aged 66 to 108, of whom the majority had mild cognitive impairment or
Alzheimer's. In this case, the SORL1 risk gene was linked with the
presence of amyloid-beta, a protein found in Alzheimer's disease.
Dr. Voineskos notes that risk for Alzheimer's disease results from a
combination of factors - unhealthy diet, lack of exercise, smoking,
high blood pressure combined with a person's genetic profile - which
all contribute to the development of the illness. "The gene has a
relatively small effect, but the changes are reliable, and may
represent one 'hit', among a pathway of hits required to develop
Alzheimer's disease later in life". While it's too early to provide
interventions that may target these changes, "individuals can take
measures in their own lifestyle to reduce the risk of late-onset
Alzheimer's disease." Determining whether there is an interaction with
this risk gene and lifestyle factors will be one important next step.
In order to develop genetically-based interventions to prevent
Alzheimer's disease, the biological pathways of other risk genes also
need to be systematically analyzed, the researchers note.
This research does, however, build on a previous CAMH imaging-genetics
study on another gene related to Alzheimer's disease. That study showed
that a genetic variation of brain-derived neurotrophic factor (BDNF)
affected brain structures in Alzheimer's.
"The interesting connection is that BDNF may have important therapeutic
value. But there is data to suggest that the effects of BDNF won't work
unless SORL1 is present, so there is the possibility that if you boost
the activity of one gene, the other will increase," says Dr. Voineskos,
adding that BDNF therapeutics are in development. A next stage in the
research, he says, is to look at the interaction of BDNF and SORL1.
SOURCE: Centre for Addiction and Mental Health
For further information:
For media enquiries please contact: Michael Torres, CAMH Media Relations, 416.595.6015 or firstname.lastname@example.org.