A new research has suggested that genetic variations linked to Alzheimer’s disease may be “at work” promoting deposits of plaque in the brain long before any symptoms of the disease can be measured on tests – a finding that could not only help further research on the disease, but could also pave way for a possible treatment.
For the study, researchers focused on people with “significant memory concerns” – adults who complained that they had mentally slipped in recent months or years, but when given standard cognition and memory tests they fell within normal ranges. People in this category have also been called the “subjective cognitive decline” group by Alzheimer’s researchers.
Using data collected as part of the national Alzheimer’s Disease Neuroimaging Initiative, study author Shannon L. Risacher, Ph.D., assistant professor of radiology and imaging sciences, and Andrew J. Saykin, Psy.D., director of the Indiana Alzheimer Disease Center and IU Center for Neuroimaging, researchers focused more intently on at-risk patients with significant memory concerns. Researchers revealed that this particular group of individuals is the logical target for the next wave of clinical trials.
The gene in question, APOE, has several variants, or “alleles.” One of those variants, APOE ?4, has been linked to an increased risk of developing Alzheimer’s disease in older adults — although not all Alzheimer’s patients have APOE ?4 alleles, and not all those who do will develop Alzheimer’s disease. APOE ?4 is common, found in about 25 percent of the population. Patients with Alzheimer’s disease who also have APOE ?4 tend to have an earlier age of onset of symptoms.
Looking at data from nearly 600 ADNI participants, the researchers compared those with the APOE ?4 variant to those with other forms of the gene. In the “significant memory concerns” group the researchers found evidence of Alzheimer’s-like pathologies from several biomarkers among the APOE ?4 carriers including:
Increased levels of amyloid plaque, the clumps of protein fragments commonly found in the brain tissue of Alzheimer’s patients.
In the cerebrospinal fluid, decreased levels of the protein precursor to the plaques, suggesting that the protein was being recruited to the brain as part of the plaque creation process.
In the cerebrospinal fluid, increased levels of tau, another protein associated with Alzheimer’s disease.
However, the analysis did not find evidence of reduced levels of glucose metabolism nor atrophy of brain structures that are associated later stages of Alzheimer’s progression.
The study provides the foundation for further focused research among patients at risk of Alzheimer’s earlier than in much other research, Dr. Risacher said.
“ADNI provides access to a wide range of biomarkers, structural and functional neuroimaging with MRI, PET scans for amyloid and for glucose metabolism, CSF biomarkers for amyloid and tau, plus genetics, and clinical and cognitive tests. No other data set has all these state-of-the-art biomarkers available for analysis,” she said.
The findings of the study have been published in the journal Alzheimer’s and Dementia.
