Study: PET can help identify genetic risk of Alzheimers
In vivo PET imaging studies of young-adult carriers of the apolipoprotein E4 allele (APOE4), the major Alzheimer’s disease susceptibility gene, have demonstrated declines in glucose metabolism in brain areas later vulnerable to Alzheimer’s disease, such as the posterior cingulate cortex, decades before the possible onset of symptoms, according to a study published in October's Journal of Alzheimer’s Disease.
This functional biomarker may prove useful in early detection and tracking of Alzheimer’s disease and indicates that mitochondrial mechanisms may contribute to the predisposition to Alzheimer’s disease before any evidence of amyloid or tau pathology, according to Jon Valla, PhD, from Barrow Neurological Institute of St. Joseph's Hospital and Medical Center in Phoenix, and colleagues.
The researchers studied tissue from a vulnerable part of the brain in 40 young adults who had died and donated their brains for research. Fifteen of the brain donors carried a common genetic risk factor for Alzheimer’s disease, known as APOE4, and 25 of the brain donors did not.
With the exception of one 34 year-old with two copies of the APOE4 gene, none of the deceased young adults had the microscopic abnormalities or elevated amyloid protein levels or tau pathology in this same region associated with Alzheimer’s disease. However, the activity of an energy-making enzyme found in the power-packs of the brain cells, cytochrome oxidase, was slightly reduced in the group at increased genetic risk for Alzheimer’s disease.
A team of researchers from several institutions in the Arizona Alzheimer’s Consortium had previously used PET imaging to detect reduced brain activity in living young adults at genetic risk for Alzheimer’s disease.
They had also shown reductions in cytochrome oxidase activity and the expression of energy-making genes in deceased brain donors with Alzheimer’s symptoms. Based on these findings, they had proposed that individuals at genetic risk for Alzheimer’s disease might have alterations in energy utilization, or some other abnormality in the mitochondria long before the progressive brain changes associated with Alzheimer’s disease had even started.
“Our findings suggest that mitochondrial brain changes contribute to the risk of Alzheimer’s disease,” said Valla. “While our findings do not suggest ways in which to predict or reduce a person’s risk at this time, they provide a foundation for studies seeking to do just that.”
This functional biomarker may prove useful in early detection and tracking of Alzheimer’s disease and indicates that mitochondrial mechanisms may contribute to the predisposition to Alzheimer’s disease before any evidence of amyloid or tau pathology, according to Jon Valla, PhD, from Barrow Neurological Institute of St. Joseph's Hospital and Medical Center in Phoenix, and colleagues.
The researchers studied tissue from a vulnerable part of the brain in 40 young adults who had died and donated their brains for research. Fifteen of the brain donors carried a common genetic risk factor for Alzheimer’s disease, known as APOE4, and 25 of the brain donors did not.
With the exception of one 34 year-old with two copies of the APOE4 gene, none of the deceased young adults had the microscopic abnormalities or elevated amyloid protein levels or tau pathology in this same region associated with Alzheimer’s disease. However, the activity of an energy-making enzyme found in the power-packs of the brain cells, cytochrome oxidase, was slightly reduced in the group at increased genetic risk for Alzheimer’s disease.
A team of researchers from several institutions in the Arizona Alzheimer’s Consortium had previously used PET imaging to detect reduced brain activity in living young adults at genetic risk for Alzheimer’s disease.
They had also shown reductions in cytochrome oxidase activity and the expression of energy-making genes in deceased brain donors with Alzheimer’s symptoms. Based on these findings, they had proposed that individuals at genetic risk for Alzheimer’s disease might have alterations in energy utilization, or some other abnormality in the mitochondria long before the progressive brain changes associated with Alzheimer’s disease had even started.
“Our findings suggest that mitochondrial brain changes contribute to the risk of Alzheimer’s disease,” said Valla. “While our findings do not suggest ways in which to predict or reduce a person’s risk at this time, they provide a foundation for studies seeking to do just that.”