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Potential of Blood-Based Alzheimer's Disease Biomarkers Demonstrated in New Study

NEW YORK (360Dx) — A combination of three biomarkers — two blood-based peptides and one genetic risk factor — can accurately predict abnormal accumulation of beta-amyloid plaques in the brains of living Alzheimer's disease patients, according to a study published online today.

The finding — which is reported in JAMA Neurology —  suggests that the biomarkers could form the basis of a blood test to prescreen subjects for inclusion in clinical Alzheimer's disease studies, offering a noninvasive and cost-effective alternative to positron emission tomography (PET) scans or lumbar punctures.

Beta-amyloid accumulation in the brain is a key hallmark of Alzheimer's disease that starts long before the onset of cognitive symptoms, but detection of this buildup in living patients is limited to PET scans and cerebrospinal fluid (CSF) analyses. While a number of promising blood-based biomarkers of beta-amyloid have been identified — including amyloid beta peptide 42, amyloid beta peptide 40, the protein tau, and neurofilament light chain (NFL) — current methods for their detection are time-consuming and expensive.

To address this issue, a research team led by scientists from Lund University aimed to test whether such biomarkers can be detected using Roche's Elecsys immunoassays, which run on the Swiss company's Cobas fully automated instrumentation, and act as effective indicators of a patient's cerebral beta-amyloid status.

The scientists analyzed plasma samples from an 842-participant cohort from the Swedish BioFINDER Study, which was launched to identify the pathological mechanisms underlying Alzheimer's disease and other neurodegenerative conditions. BioFINDER includes individuals of different ages with mild cognitive symptoms, Alzheimer's disease patients, and controls. They also studied samples from independent validation cohort of 237 individuals — including ones with mild cognitive impairment and Alzheimer's disease, as well as unimpaired controls — from a German biomarker study.

For the BioFINDER cohort, the scientists used Elecsys assays to detect amyloid beta peptide 42, amyloid beta peptide 40, tau, NFL, and neurofilament heavy chain. The validation cohort focused on amyloid beta peptide 42, amyloid beta peptide 40, and tau.

The researchers found that plasma amyloid beta peptide 42 and amyloid beta peptide 40 as measured on the Elecsys assays accurately predicted cerebral beta-amyloid status with an area under the receiver operating characteristic curve (AUC) of .80. Notably, the addition of the apolipoprotein E genotype — which has been linked to Alzheimer's disease, dementia, and cardiovascular disease — had a significant impact on accuracy, increasing the AUC to .85. The results, they added, were similar in cognitively unimpaired and cognitively impaired participants across age range.

The investigators then performed a cost-benefit analysis of a clinical trial scenario involving 1,000 beta-amyloid-positive individuals and a PET screening cost of $4,000 per participant. Using amyloid beta peptide 42, amyloid beta peptide 40, and the APOE genotype screening, they found, could lower PET costs up to 50 percent.

Based on these results, the study's authors suggest that future optimized beta-amyloid assays offer the most promise as a screening tool for identifying high-risk individuals, providing physicians with additional information to guide decisions to refer patients for more extensive clinical assessment. Another potentially useful application for the assays would be in prescreening enrollees for clinical Alzheimer's disease trials in order to minimize unnecessary lumbar punctures and PET scans, and lower examination costs.

The findings, University of North Texas Health Science Center researcher Sid O'Bryant wrote in an editorial accompanying the study, "demonstrate that the field is rapidly moving from if blood biomarkers can be used in [Alzheimer's disease] to how they can be used. This work demonstrates the superiority of automated technologies, and the findings provide a solid foundation on which to build."