The risk of Alzheimer's disease from childhood

A new study shows that the risk gene for Alzheimer's disease can begin to affect the brain from childhood.

People with a high-risk gene for Alzheimer's disease show that their brain changes began in childhood, decades before the disease appeared, a new study by scientists from Center for Addiction and Mental Health Center (CAMH) announced.

This gene, called SORL1 , is one of the genes involved in increasing late Azheimer's disease, the most common form of the disease. SORL1 brings gene receptors like sortilin , involved in the recycling of certain molecules in the brain before they develop into beta - amyloid, a toxic Azheimer protein . SORL1 is also involved in lipid metabolism.

'We need to understand where, and when, as well as how the risk genes for Alzheimer's affect the brain, by studying biological pathways through which these genes are works, ' said Dr. Aristotle Voineskos, head of the Kimel Family Translational Imaging-Genetics Laboratory at CAMH. 'Through this knowledge, we can start designing interventions at the right time, for the right people'.

The study is now presented online in Molecular Psychiatry with graduate students of Dr. Voineskos, Daniel Felsky is the first author, and a collaborative supporter with Zucker Hillside Hospital / Feinstein Institute research institute. in New York and Rush Alzheimer's Disease Center in Chicago.

To understand the effect of SORL1 on life expectancy, scientists have studied individuals who are ill and not Alzheimer's. Their approach is to identify genetic differences in SORL1, and consider whether there is a link to Alzheimer's disease related to changes in the brain, using image analyzes as well. like brain tissue analysis.

In each approach, a link has been confirmed.

In the first group of healthy people, ages 8 to 86, researchers used a brain imaging technique called tensor diffuse imaging (diffusion tensor imaging (DTI). Even in lesser people. The oldest in this study, those with a specific copy of the SORL1 gene showed that a decline in white matter connections in the brain region is important for the memory capacity and executive function of Brain.

The second sample contains the brain tissue of 189 individuals under one year of age until 92 years old, without Alzheimer's disease. Among those with the same copy of SORL1, brain tissue showed a disruption in the process that somehow its gene transcribed to become receptor like sortilin.

Finally, the third group includes samples from 710 people, ages 66 to 108, most of whom have mild cognitive impairment or Azheimer.

Dr. Voineskos noted that the risk of developing Alzheimer's disease is the result of many factors such as unhealthy diet, no exercise, smoking, high blood pressure combined with genetic history - all They all contribute to the development of this disease.'This gene has a relatively small effect, but the changes are very solid, and may represent a' blow 'in a series of strokes leading to Alzheimer's development in later life.' .

While it is still too early to provide intervention to address these changes, 'individuals can assess and change their own lifestyles to reduce the risk of developing Alzheimer's disease'. Determining whether or not there is an interaction between this risk gene and lifestyle factors will be an important next step.

The researchers note that, in order to develop genetic-based interventions to prevent Alzheimer's disease, biological pathways of other risk genes need to be systematically analyzed.

The study is based on genetic studies using imaging techniques on another gene linked to Alzheimer's disease. That study has shown a genetic variation of brain-derived neurological nutritional factors (BDNF) that affect brain structure in Alzheimer's disease.

"The interesting connection is that BDNF may have important therapeutic value. But there are data that show that the effects of BDNF will not work unless SORL1 is present, so it is possible that If you increase the activity of one gene, the activity of another gene will also increase, " Dr. Voineskos said, adding that BDNF therapy is currently being developed. The next stage in research, Voineskos says, is to look at the interaction between BDNF and SORL1.