Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care
Open accessAbstract
Importance: An accurate blood test for Alzheimer disease (AD) could streamline the diagnostic workup and treatment of AD. Objective: To prospectively evaluate a clinically available AD blood test in primary care and secondary care using predefined biomarker cutoff values. Design, Setting, and Participants: There were 1213 patients undergoing clinical evaluation due to cognitive symptoms who were examined between February 2020 and January 2024 in Sweden. The biomarker cutoff values had been established in an independent cohort and were applied to a primary care cohort (n = 307) and a secondary care cohort (n = 300); 1 plasma sample per patient was analyzed as part of a single batch for each cohort. The blood test was then evaluated prospectively in the primary care cohort (n = 208) and in the secondary care cohort (n = 398); 1 plasma sample per patient was sent for analysis within 2 weeks of collection. Exposure: Blood tests based on plasma analyses by mass spectrometry to determine the ratio of plasma phosphorylated tau 217 (p-tau217) to non–p-tau217 (expressed as percentage of p-tau217) alone and when combined with the amyloid-β 42 and amyloid-β 40 (Aβ42:Aβ40) plasma ratio (the amyloid probability score 2 [APS2]). Main Outcomes and Measures: The primary outcome was AD pathology (determined by abnormal cerebrospinal fluid Aβ42:Aβ40 ratio and p-tau217). The secondary outcome was clinical AD. The positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and area under the curve (AUC) values were calculated. Results: The mean age was 74.2 years (SD, 8.3 years), 48% were women, 23% had subjective cognitive decline, 44% had mild cognitive impairment, and 33% had dementia. In both the primary care and secondary care assessments, 50% of patients had AD pathology. When the plasma samples were analyzed in a single batch in the primary care cohort, the AUC was 0.97 (95% CI, 0.95-0.99) when the APS2 was used, the PPV was 91% (95% CI, 87%-96%), and the NPV was 92% (95% CI, 87%-96%); in the secondary care cohort, the AUC was 0.96 (95% CI, 0.94-0.98) when the APS2 was used, the PPV was 88% (95% CI, 83%-93%), and the NPV was 87% (95% CI, 82%-93%). When the plasma samples were analyzed prospectively (biweekly) in the primary care cohort, the AUC was 0.96 (95% CI, 0.94-0.98) when the APS2 was used, the PPV was 88% (95% CI, 81%-94%), and the NPV was 90% (95% CI, 84%-96%); in the secondary care cohort, the AUC was 0.97 (95% CI, 0.95-0.98) when the APS2 was used, the PPV was 91% (95% CI, 87%-95%), and the NPV was 91% (95% CI, 87%-95%). The diagnostic accuracy was high in the 4 cohorts (range, 88%-92%). Primary care physicians had a diagnostic accuracy of 61% (95% CI, 53%-69%) for identifying clinical AD after clinical examination, cognitive testing, and a computed tomographic scan vs 91% (95% CI, 86%-96%) using the APS2. Dementia specialists had a diagnostic accuracy of 73% (95% CI, 68%-79%) vs 91% (95% CI, 88%-95%) using the APS2. In the overall population, the diagnostic accuracy using the APS2 (90% [95% CI, 88%-92%]) was not different from the diagnostic accuracy using the percentage of p-tau217 alone (90% [95% CI, 88%-91%]). Conclusions and Relevance: The APS2 and percentage of p-tau217 alone had high diagnostic accuracy for identifying AD among individuals with cognitive symptoms in primary and secondary care using predefined cutoff values. Future studies should evaluate how the use of blood tests for these biomarkers influences clinical care.
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Plasma biomarkers are likely to play an important role in future AD diagnostics due to their low cost and high accuracy, and recent work has evaluated them in primary care.
“Plasma biomarkers are not yet broadly available, but due to their low cost and high accuracy, they are likely to play an important role in future AD diagnostics. Recent work has successfully evaluated them in primary care, highlighting their potential for broad clinical use. 51”
From Machine learning prediction of tau‐PET in Alzheimer's disease using plasma, MRI, and clinical data (2025) · cites this paper as [51]
The comparison of biomarkers in primary and secondary care (page not provided) reports about 90% accuracy for two plasma-based tests in primary care, supporting the claim that they were successfully evaluated there and have diagnostic potential. The passages do not establish that these tests are low-cost or not yet broadly available, so those parts of the citing sentence are unsupported. (LLM, conf=0.84)
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- Authors
- Palmqvist, S., Tideman, P., Mattsson-Carlgren, N., Schindler, S. E., Smith, R., Ossenkoppele, R., Calling, S., West, T., Monane, M., Verghese, P. B., Braunstein, J. B., Blennow, K., Janelidze, S., Stomrud, E., Salvadó, G., & Hansson, O.
- Affiliations
- Lund University (SE)
- Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden
- Washington University in St. Louis (US)
- C2N Diagnostics (United States) (US)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Palmqvist, Sebastian
- Hansson, Oskar
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2024-10-15
- Volume
- 332
- Issue
- 15
- Pages
- 1245
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC11284636
- OpenAlex
- W4401062865
- Cited by
- 416
- References
- 44
- Citations by year
- 2026: 202 · 2025: 173 · 2024: 40 · 2021: 1
- FWCI
- 121.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Funders
- National Institute on Aging (R01AG083740)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- Alzheimer's disease, blood biomarkers, diagnostic accuracy, primary care, secondary care, cerebrospinal fluid biomarkers, mild cognitive impairment, dementia, mass spectrometry, positive predictive value
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Peptide Fragments, Phosphorylation, Primary Health Care, Prospective Studies, Sensitivity and Specificity, Sweden, Biomarkers, Amyloid beta-Peptides, tau Proteins, Cognitive Dysfunction, Secondary Care, Secondary Health Care
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