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. (Agencies)
SORL1 carries the gene code for the sortilin-like receptor, which is involved in recycling some molecules in the brain before they develop into the toxic beta-amyloid protein.
To understand SORL1's effects across the lifespan, the researchers, including Aristotle Voineskos, head of the Kimel Family Translational Imaging-Genetics Laboratory at Canada's
Centre for Addiction and Mental Health (CAMH), 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 protein found in Alzheimer's.
Voineskos noted 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," Voineskos said.
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", researchers said.
Determining whether there is an interaction with this risk gene and lifestyle factors will be one important next step, they added.
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.