Alzheimer’s Disease (AD) is the most common cause of dementia and accounts for an estimated 60% to 80% of cases.
1 It is now known that these brain changes are thought to begin 20 years or more before symptoms appear.
2-4 Even though the need for an early diagnosis has been established, AD remains a diagnostically challenging disease for providers.
5
Just a little over two decades ago, the diagnosis of AD was made through autopsy. Today, pathology is much better understood, and diagnosis is often made through a combination of clinical signs, biomarkers in cerebrospinal fluid (CSF), and amyloid PET scans. However, many of these tests can bring their own challenges and may be costly for patients. Along with a better understanding of typical and atypical AD and dementia phenotypes, the addition of AD biomarkers to the clinical paradigm allows for an earlier diagnosis of patients who present with a variety of clinical presentations.
6New disease-modifying treatments have been shown to impact the underlying AD pathology but are likely most beneficial in early AD.
7,8
Current research indicates that plasma pTau, including pTau-217, is associated with the development of AD neurofibrillary tangles and is a predictor of amyloid status determined either by CSF
9 or PET
10, and therefore able to differentiate between AD and non-AD neurodegenerative diseases and to predict progression to AD.
11,12 β-Amyloid 1-42 is a protein that forms plaques in the brain during AD and can be detected years before the onset of AD symptoms, indicating a significant role in the pathogenesis of AD.
13 While previously only available as CSF assays, a plasma ratio assay for these biomarkers has recently been recently approved by the FDA as a first approved plasma-based biomarker diagnostic test for AD. Plasma biomarker assays may assist in the diagnosis of AD along with other clinical measures and are more readily available and affordable than CSF tests. These biomarkers could advance the development and implementation of disease-modifying treatments in the field of AD and related disorders.
14,15
Plasma-based AD biomarker tests were only recently approved and many clinicians are not aware of their availability or use within a clinical diagnostic algorithm. This program will provide participants with information regarding the development and interpretation of plasma biomarkers for AD diagnosis, as well as their role for both primary care providers and neurologists within a clinical diagnostic paradigm.
References
1. Alzheimer’s Association. 2024 Alzheimer’s disease facts and figures. Alzheimers Dement. 2024;20(5):3708-3821.
2. Reiman EM, Quiroz YT, Fleisher AS, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer’s disease in the presenilin 1 E280A kindred: A case-control study. Lancet Neurol 2012;11(2):1048-56.
3. Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012;367(9):795-804.
4. Gordon BA, Blazey TM, Su Y, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study. Lancet Neurol 2018;17(3):241-50.
5. Giebel C, Silva-Ribeiro W, Watson J, et al. A systematic review on the evidence of misdiagnosis in dementia and its Impact on accessing dementia care. Int J Geriatr Psychiatry 2024 Oct;39(10):e6158.
6. Dubois B, von Arnim CAF, Burnie N, et al. Biomarkers in Alzheimer's disease: role in early and differential diagnosis and recognition of atypical variants. Alzheimers Res Ther 2023 Oct 13;15(1):175.
7. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease. Accessed 11 March 2025.
8. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval. Accessed 11 March 2025.
9. Mielke M, Dage JL, Frank RD, et al. Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med. 2022;28(7):1398-1405.
10. Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho-tau 217 for Alzheimer’s disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772-781.
11. Thijssen EH, La Joie R, Strom A, et al. Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol 2021;20(9):739-752.
12. Jonaitis EM, Janelidze S, Cody KA, et al. Plasma phosphorylated tau 217 in preclinical Alzheimer’s disease. Brain Commun 2023;5(2):fcad057.
13. Mayeux R, et al. Plasma amyloid β-peptide 1–42 and incipient Alzheimer's disease. Ann Neurol 2001;46(3):412-416.
14. Mattsson-Carlgren N, et al. Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers. JAMA Neurol 2023;80(4):360-369.
15. Gonzalez-Ortiz F, Kac PR, Brum WS,et al. Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications. Mol Neurodegener 2023;18(1):18.
