Blood Tests for Alzheimer’s Are Here…Are Clinicians Ready?

With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease (AD), the need for accurate and early diagnosis is crucial.

Blood-based biomarkers offer a promising alternative to amyloid PET scans and cerebrospinal fluid (CSF) analysis and are being increasingly used in clinical practice to support an AD diagnosis.

Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of AD blood-based biomarkers.

“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina, told Medscape Medical News.

Triage and Confirmatory Pathways

The group recommends two implementation pathways for AD blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.

In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–AD-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.

A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.

In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.

Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the AD blood biomarkers in clinical care increase and additional barriers and facilitators are identified.

“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” workgroup co-chair Chi Udeh–Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya, told Medscape Medical News.

The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.

“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association, told Medscape Medical News.

“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.

Availability and Accuracy

Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying AD in patients with cognitive symptoms attending primary and secondary care clinics.

Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.

In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with AD outcomes.

A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified AD.

“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.

New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.

Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”

“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she told Medscape Medical News.

There are also emerging biomarkers in the research pipeline, Edelmayer said.

“For example, some researchers think retinal imaging has the potential to detect biological signs of AD within certain areas of the eye,” she explained.

“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer told Medscape Medical News.

Ideal Candidates for AD Blood Testing?

Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.

At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.

She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”

“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.

Ethical Considerations, Counseling

Elahi emphasized the importance of counseling patients who come to the clinic seeking an AD blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.

Elahi said patients need to be informed that AD blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”

To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.

Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”

Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.