Alzheimer’s Disease Biomarker Advances: Plasma
Although PET and CSF biomarkers were accurate in detecting amyloid pathology, the technology was expensive, invasive, and not widely available. In the late 2010s, researchers found that phosphorylated tau from blood plasma (specifically p-tau181) could accurately predict amyloid pathology and identify Alzheimer’s disease. In 2019, researchers also found that neurofilament light (NfL) in blood samples was associated with neurodegeneration and could be used to monitor both the effects of drug interventions and further neurodegeneration.
Blood draws are routine in clinical care and there are established processes for collecting, storing, and handling blood samples. The introduction of a blood plasma based biomarker for Alzheimer’s disease not only increased the accessibility of screening, diagnosis, and treatment monitoring, but it also helped facilitate the large-scale studies and longitudinal monitoring needed to identify rare genetic variants, refine phenotypes, observe gene-environment interactions, and validate previous genetic findings.
REFERENCES
- In 2018, an international working group published an overview of their assessment of blood-based biomarkers for Alzheimer’s disease in Nature Reviews Neurology. The working group considered the importance of a more accessible biomarker for clinical and research settings, the validation process needed to determine its efficacy, and the research priorities that would further evaluate its widespread use.
Hampel H, O’Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S, Kiddle SJ, Batrla R, Blennow K. Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Nat Rev Neurol. 2018 Nov;14(11):639-652. https://doi.org/10.1038/s41582-018-0079-7
- In 2020, a study published in JAMA Neurology demonstrated that plasma p-tau181 could be reliably measured in blood plasma and was associated with amyloid positivity and the likelihood of Alzheimer’s disease. The study also highlighted the potential use of plasma p-tau181 in primary care settings.
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, Chamoun M, Savard M, Kang MS, Therriault J, Schöll M, Massarweh G, Soucy JP, Höglund K, Brinkmalm G, Mattsson N, Palmqvist S, Gauthier S, Stomrud E, Zetterberg H, Hansson O, Rosa-Neto P, Blennow K. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020 May;19(5):422-433. https://doi.org/10.1016/S1474-4422(20)30071-5
- A 2019 study in Nature Medicine showed that NfL in blood plasma could be an effective biomarker for the presence and progression of neurodegeneration associated with Alzheimer’s disease.
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2019 Jul 1;76(7):791-799. https://doi.org/10.1001/jamaneurol.2019.0765Bottom of Form