Alzheimer disease blood biomarkers: considerations for population-level use

• Published in: Nature reviews. Neurology 2024-08, Vol.20 (8), p.495-504
• Main Authors: Mielke, Michelle M., Fowler, Nicole R.
• Format: Article
• Language: English
• Subjects: 692/53; 692/617/375/132/1283; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Cognitive Dysfunction - blood; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Ethnicity; Humans; Medicine; Medicine & Public Health; Neurology; Review Article
• ISSN: 1759-4758; 1759-4766; 1759-4766
• DOI: 10.1038/s41582-024-00989-1

In the past 5 years, we have witnessed the first approved Alzheimer disease (AD) disease-modifying therapy and the development of blood-based biomarkers (BBMs) to aid the diagnosis of AD. For many reasons, including accessibility, invasiveness and cost, BBMs are more acceptable and feasible for patients than a lumbar puncture (for cerebrospinal fluid collection) or neuroimaging. However, many questions remain regarding how best to utilize BBMs at the population level. In this Review, we outline the factors that warrant consideration for the widespread implementation and interpretation of AD BBMs. To set the scene, we review the current use of biomarkers, including BBMs, in AD. We go on to describe the characteristics of typical patients with cognitive impairment in primary care, who often differ from the patient populations used in AD BBM research studies. We also consider factors that might affect the interpretation of BBM tests, such as comorbidities, sex and race or ethnicity. We conclude by discussing broader issues such as ethics, patient and provider preference, incidental findings and dealing with indeterminate results and imperfect accuracy in implementing BBMs at the population level. Blood-based biomarkers have the potential to transform the Alzheimer disease diagnostic pathway, but many questions remain regarding their implementation and utilization. This Review considers factors that might affect the interpretation of blood-based biomarker tests, including comorbidities, sex and race or ethnicity, and discusses broader issues surrounding their use at the population level. Key points Numerous studies have demonstrated the clinical utility and accuracy of plasma measures of the amyloid-β 42:40 ratio and phosphorylated tau (p-tau) 181 and p-tau217 levels for the detection of Alzheimer disease (AD) pathology among clinically well-characterized patients. Most AD blood-based biomarker (BBM) studies focused on specialty clinic populations are not generalizable to typical patients with dementia, and an urgent need exists to test the BBMs at the population level. Chronic kidney disease, obesity and cardiovascular conditions or medication can elevate or lower AD BBM levels and need to be taken into consideration to avoid false-positive or false-negative diagnoses; understanding how to interpret AD BBM levels in the context of multiple chronic conditions is crucial for diagnosing AD among older adults in the population. Other factors that might influence