Alzheimer’s Blood Tests: Not Ready for Primary CareAugust 4, 2022
Blood biomarkers may change how Alzheimer’s disease is diagnosed but aren’t ready for widespread use in primary care yet, a panel of experts said.
“The field of blood-based biomarkers is moving very, very fast,” said Oskar Hansson, MD, PhD, of Lund University in Malmö, Sweden, who presented the Alzheimer’s Association’s appropriate use recommendations for blood biomarkers at the 2022 Alzheimer’s Association International Conference.
The recommendations, published in Alzheimer’s & Dementia, are not appropriate use criteria, Hansson noted. “It’s likely we will need to update these recommendations within 12 months.”
The Alzheimer’s Association working group of clinicians and researchers did not recommend blood-based biomarkers for population risk screening or as direct-to-consumer tests at this time.
“However, blood-based biomarkers are very likely to revolutionize the diagnosis of Alzheimer’s in the future,” Hansson said.
In the report, the group recognized a significant unmet need for better diagnostic tools, noting that 25% to 30% of people who receive a clinical diagnosis of Alzheimer’s are misdiagnosed.
“Misdiagnosis of Alzheimer’s is far too common,” said Maria Carrillo, PhD, chief science officer of the Alzheimer’s Association.
“Blood-based markers show promise for improving the diagnostic work-up for Alzheimer’s, but additional data are needed before they can be used as a stand-alone test for diagnosis, and before considering broad use in primary care settings,” she added.
The group provided recommendations for plasma amyloid-beta 42/amyloid-beta 40 (Aβ42/Aβ40), phospho-tau (p-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and potential combinations of markers.
Some of these biomarkers, especially Aβ42/Aβ40 and p-tau, are changing how clinical trials are designed, Hansson noted.
But even in clinical trials, caution is warranted, he pointed out. Blood biomarkers can be used as exploratory outcomes, but should not yet be used as primary endpoints in pivotal treatment trials. They also may help inform decisions about whether some clinical trials should be continued or help identify patients who may have Alzheimer’s-related brain pathology in non-Alzheimer’s trials.
The group also identified what research is needed to fill knowledge gaps, including how well blood markers work in diverse populations and in people with multiple health conditions. In addition, no studies have evaluated blood-based biomarkers for neurodegenerative diseases in primary care extensively. How these biomarkers may influence diagnostic accuracy and patient management also is unknown.
The Alzheimer’s Association workgroup called for:
- Prospective studies in primary care settings, including representative and diverse populations with cognitive symptoms.
- Analyses to determine whether blood biomarkers outperform what is already available in primary care and whether they improve diagnosis and management.
- Better understanding of biological and disease-associated variability and the potential effects of medical comorbidities and concomitant medications on dementia
- An assessment of whether blood biomarker algorithms can be used alone to support an Alzheimer’s diagnosis or whether additional cerebrospinal fluid (CSF) and PET studies are needed.
“We also recommend cautiously starting use of blood-based biomarkers in specialized memory clinics as part of the diagnostic work-up of patients already experiencing cognitive symptoms, as long as the results are confirmed whenever possible with CSF or PET, which are the current reference standards,” said workgroup member Charlotte Teunissen, MD, PhD, of Amsterdam University Medical Center in the Netherlands.
Blood-based biomarkers in primary care will take longer to implement due to limited research to date, but prospective studies are launching soon, she added.
Hansson disclosed institutional research support from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has also received consultancy/speaker fees from Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Fujirebio, Genentech, Novartis, Roche, and Siemens.
Teunissen has a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly, and has performed contract research or received grants from AC-Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, and Vivoryon.
Carrillo is a full-time employee of the Alzheimer’s Association.