Detecting Alzheimer's Disease Seventeen Years in Advance
Alzheimer's disease develops over twenty years or more, a slow growth of amyloid-β aggregates in the brain that sets the stage for a feedback loop of inflammation, cellular senescence, and tau aggregation that causes severe pathology and eventual death. As researchers demonstrate here, patients who will very likely go on to develop Alzheimer's disease many years in the future can be identified quite early. The mechanisms that will inexorably lead to the condition, and the lifestyle choices that adjust the pace of progress, are in place as much as two decades prior to diagnosis with the clinical stage of the disease. This produces signatures in the bloodstream that can be seen with simple tests, or at least the tests are simple once those signatures have been identified. It is that identification that has proven challenging, but the research community has made rapid progress on this front in the past few years.
The dementia disorder Alzheimer's disease has a symptom-free course of 15 to 20 years before the first clinical symptoms emerge. Using an immuno-infrared sensor, a research team is able to identify signs of Alzheimer's disease in the blood up to 17 years before the first clinical symptoms appear. The sensor detects the misfolding of the protein biomarker amyloid-beta. As the disease progresses, this misfolding causes characteristic deposits in the brain, so-called plaques.
The researchers analysed blood plasma from participants in the ESTHER study for potential Alzheimer's biomarkers. The blood samples had been taken between 2000 and 2002 and then frozen. At that time, the test participants were between 50 and 75 years old and hadn't yet been diagnosed with Alzheimer's disease. For the current study, 68 participants were selected who had been diagnosed with Alzheimer's disease during the 17-year follow-up and compared with 240 control subjects without such a diagnosis. The team aimed to find out whether signs of Alzheimer's disease could already be found in the blood samples at the beginning of the study.
The immuno-infrared sensor was able to identify the 68 test subjects who later developed Alzheimer's disease with a high degree of test accuracy. For comparison, the researchers examined other biomarkers with the complementary, highly sensitive SIMOA technology - specifically the P-tau181 biomarker, which is currently being proposed as a promising biomarker candidate in various studies. "Unlike in the clinical phase, however, this marker is not suitable for the early symptom-free phase of Alzheimer's disease. Surprisingly, we found that the concentration of glial fibre protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor." Still, by combining amyloid-beta misfolding and GFAP concentration, the researchers were able to further increase the accuracy of the test in the symptom-free stage.