Alzheimer’s Blood Test Guidelines Aim to Standardize Clinical Use
New recommendations from the Alzheimer’s Association call for Alzheimer’s blood tests to reach at least 90% sensitivity and specificity to be used in place of established diagnostic tools.
Alzheimer’s blood tests need to offer at least 90% sensitivity and 90% specificity before they can replace brain scans and spinal taps in diagnosis of the neurodegenerative disease, according to a new clinical practice guideline recommendation from the Alzheimer’s Association.
The health organization cautioned in a news release that “many commercially available blood-based biomarker tests do not meet these thresholds” for substituting amyloid PET imaging and cerebrospinal fluid (CSF) tests in Alzheimer’s diagnosis.
“The whole purpose of developing the clinical practice guideline is to try to create pragmatic recommendations for clinicians on how to choose the right test for the right patient at the right time,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, told Medscape. “The blood- based biomarker area is still a burgeoning field,” added Edelmayer, a guideline Co-author.
Clinical laboratories may find the recommendations useful in making decisions about additions to lab test menus and in educating clinicians on appropriate test ordering.
Pathological Signs of Alzheimer’s
Edelmayer and colleagues published the guideline in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, entitled, “Alzheimer’s Association Clinical Practice Guideline on the Use of Blood-Based Biomarkers in the Diagnostic Workup of Suspected Alzheimer’s Disease Within Specialized Care Settings.”
“Pathologically, Alzheimer’s disease is defined by the accumulation of extracellular cortical plaques composed of amyloid-beta fibrils and intracellular neurofibrillary tangles containing abnormal hyperphosphorylated tau protein. These pathologies manifest many years or even decades before the onset of clinical symptoms,” the authors wrote.
Compared to “standard-of-care” amyloid PET imaging and CSF tests, blood-based biomarkers may cost less and reduce patients’ stress, the Alzheimer’s Association pointed out, adding that blood tests are not a replacement for clinical evaluations by healthcare providers.
“What we’ve learned from all of the evidence so far is that some of these biomarkers, like tau217, tend to be very accurate predictors of Alzheimer’s disease biology in the brain, and they can be used to aid in the diagnostic process early on—sometimes even before tau tangle formations can be visualized with brain imaging,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, said in the Medscape article. (Photo credit: Alzheimer’s Association.)
Panel Reviews Phosphorylated-tau and Amyloid-beta
To discover the diagnostic accuracy of blood-based biomarkers in Alzheimer’s disease, a panel of 11 clinicians, convened by the Alzheimer’s Association, did a systematic review using this methodology described in the association’s statement:
- Reviewed 49 observational studies and assessed 31 tests.
- Focused on blood-based biomarkers including plasma phosphorylated-tau (p-tau) and amyloid beta (Aβ) tests measuring: p-tau217, ratio of p-tau217 to non-p-tau217 x 100, p-tau181, p-tau231, and ratio of Aβ42 to Aβ40.
- Applied Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to “evaluate certainty of evidence” and aid development of recommendations.
- Panelists, unaware of the tests they were reviewing, did not rank or endorse tests.
Diagnostic accuracy varied among the assays with sensitivity ranging from 49.31% to 91.41% and specificity from 61.54% to 96.72%, Neurology Advisor reported.
Tests evaluated included these, which were also recently reported on by Dark Daily:
Elecys by Roche, Lumipulse created by Fujirebio, and Precivity from C₂N Diagnostics.
Advice for Using Alzheimer’s Blood Tests
Based on the systematic review, the panel released the following recommendations for use of blood-based biomarker tests when Alzheimer’s disease is suspected, according to the Alzheimer’s Association:
- Tests with 90% sensitivity and 90% specificity or more may stand-in for PET amyloid imaging or CSF Alzheimer’s biomarker testing.
- Tests with at least 90% sensitivity and 75% specificity can serve as triaging assays whereby negative results rule out Alzheimer’s “with high probability” while positive findings need confirmation with PET or CSF testing.
“For the first time, we have a rigorously evidence-based guideline that empowers clinicians to use blood biomarker tests confidently and consistently. Adoption of these recommendations will lead to quicker, more accessible, more accurate diagnoses, and better outcomes,” said Maria Carillo, PhD, Alzheimer’s Association Chief Science Officer and Medical Affairs Lead and a Co-author of the guideline.
The guideline is part of the Alzheimer’s Association resources to promote best practices. It plans development of other reports about cognitive assessment tools, clinical implementation of staging, and Alzheimer’s prevention.
—Donna Marie Pocius
