Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 60%-80% of cases, with 7.2 million Americans affected in 2025 and the number projected to double by 2060.¹ Diagnostic confirmation has traditionally relied on cerebrospinal fluid (CSF) analysis or positron emission tomography (PET) imaging, both of which are costly, invasive and often unavailable in routine practice.¹ These limitations increase the risk of misdiagnosis and delay access to amyloid-targeting therapies that require biomarker confirmation.¹ To address this gap, the Alzheimer’s Association has released its first clinical practice guideline (CPG) on blood-based biomarker (BBM) tests, establishing evidence-based recommendations for their use in the diagnostic workup of suspected AD in specialized care settings.¹

Considerable progress has been made in developing BBMs for AD, with plasma phosphorylated tau (p-tau) and amyloid-beta (Aβ) assays showing high concordance with CSF and PET measures, offering a scalable alternative for earlier detection.^2-4 BBM tests are minimally invasive and reduce the discomfort and anxiety associated with lumbar puncture or PET procedures.¹ BBM tests streamline diagnosis, enable earlier identification of AD pathology and treatment initiation, while reducing the burden on patients, caregivers and the healthcare system.¹ However, heterogeneous assay performance across platforms and population diversity further complicates interpretation, highlighting the need for standardized, evidence-based recommendations.^1-3 This guideline supports clinical decision-making, standards of care, laboratory practices, and integrate BBMs into clinical practice.¹

The CPG was developed by the Alzheimer’s Association through a multidisciplinary expert panel comprising neurologists, geriatricians, advanced practice providers, and methodologists, based on a systematic review of 49 observational studies encompassing 31 BBM assays.¹ BBM test was defined as a specific analyte measured using a particular technology, with focus on plasma p-tau (p-tau217, %p-tau217, p-tau181, p-tau231) and Aβ42/Aβ40 assays selected for their strong evidence base and high diagnostic accuracy, while less-established biomarkers were excluded.¹ BBM performance was validated against CSF biomarkers, amyloid PET or neuropathology.¹

The panel adhered to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, evaluating diagnostic accuracy, certainty of evidence, balance of benefits and harms, patient values and preferences, feasibility, cost-effectiveness, and equity.¹ Recommendations were formulated to be brand-agnostic and defined according to diagnostic accuracy thresholds, with tests considered accurate for triaging if sensitivity ≥90% and specificity ≥75%, and for confirmatory use if both were ≥90%.¹

The guideline provides recommendations for patients with objective cognitive impairment, including mild cognitive impairment or dementia, under specialized memory care settings.¹ The panel concluded that BBM assays with ≥90% sensitivity and ≥75% specificity can be used as a triaging tool for AD pathology.¹ A negative result reliably excludes AD-related changes, reducing the need for invasive CSF or costly PET testing, while a positive result requires confirmation with established biomarkers.¹ Assays with ≥90% sensitivity and specificity may substitute for CSF or PET for diagnostic confirmation, potentially expanding access to timely diagnosis.¹

The panel emphasized that BBM testing does not replace a comprehensive clinical evaluation by a healthcare professional and should be interpreted alongside clinical assessment, cognitive testing, patient history, and pre-test probability, as part of a full diagnostic workup for patients.¹ The panel also highlighted that BBM assays are not interchangeable, as performance varies by assay design and validation.¹ The guideline is intended to be regularly updated, with the associated systematic review revised as new evidence emerges to maintain clinical relevance over time.¹

In summary, BBMs offer a patient-friendly option that can expand diagnostic reach and improve access to timely care, especially among older adults and underserved populations.¹ The Alzheimer’s Association CPG provides clinicians with the first structured roadmap for BBM use by defining triage and confirmatory accuracy thresholds, while emphasizing integration into the diagnostic workflow within an evolving framework.¹