A newly-developed blood test could help tell who’s at risk of developing Alzheimer’s before the onset of symptoms. The research focused on patients who were clinically diagnosed as not having Alzheimer’s, but perceived themselves as being cognitively impaired — a condition known as Subjective Cognitive Decline, SCD. The goal was to see whether a new type of test could tell which of these patients were at risk of developing Alzheimer’s later on. So far, the findings are very encouraging: the test managed to pinpoint during the study all 22 subjects who developed Alzheimer’s dementia, thus the clinical symptoms, within six years. It further identified those participants who were at very low risk of developing it as well. Testing for the future The authors, a joint German-Dutch research team worked with 203 participants, taking samples of their blood and analyzing these through an immuno-infrared sensor for misfolding of the amyloid-beta (Aβ) peptides — a known biomarker for Alzheimer’s disease. They were also extensively tested for Alzheimer’s, proving that none of the participants had developed the condition at the study’s onset. However, testing revealed misfolded Aβ peptides at this point in 22 participants, all of whom developed clinical Alzheimer’s in the six years after the study. For patients with mild misfolding, onset of clinical Alzheimer’s took longer on average (3.4 years) than for subjects with severe Aβ misfolding (2.2 years). The researchers used these figures to predict the risk of each participant developing clinical Alzheimer’s disease using a statistical model. This suggested that participants with SCD and mild misfolding have an 11-fold higher risk of developing the condition, while those with SCD and severe misfolding were 19 times as likely to develop clinical Alzheimer’s than the other participants. “Misfolding of Aβ is therefore a very precise prognostic plasma biomarker,” concludes biophysics Professor Klaus Gerwert from the Bochum Research Center for Protein Diagnostics, lead researcher of the paper. They further checked whether their predictions could be improved by looking at the combination of two different measurement methods for Alzhimer’s biomarkers — the level of misfolding of all Aβ isoforms alongside the ratio of Aβ42 to Aβ40 in plasma. This did increase the accuracy of the predictions statistically, the team explains. “We can now very accurately predict the risk of developing clinical Alzheimer’s disease in the future, with a simple blood test on symptom-free individuals with subjective concerns,” explains Gerwert. “However, we can just as confidently give the all-clear for SCD patients who have a very low probability of developing Alzheimer’s disease in the next six years.” The test can also be used to “monitor disease progression over 14 years”, starting frim the asymptomatic stage all the way to clinical onset, says Julia Stockmann of the Bochum Research Center for Protein Diagnostics, co-lead author of the paper. Such a test is an essential half of a working strategy against Alzheimer’s. Once we’re able to actually treat the condition (there are some drugs in the works that may serve this purpose, such as aducanumab, still in testing with the U.S. Food and Drug Administration), such a test can be used to tell who is most in need of treatment, potentially saving thousands of lives from a debilitating condition. “Our results indicate that Alzheimer’s drugs should be applied as early as possible in a non-clinical stage to improve therapy response,” Gerwert said. The paper “Amyloid-β misfolding as a plasma biomarker indicates risk for future clinical Alzheimer’s disease in individuals with subjective cognitive decline” has been published in the journal Alzheimer’s Research & Therapy. Source
