Plasma Biomarker Applications in Alzheimer's Disease Diagnostics

Plasma biomarkers offer minimally invasive and scalable approaches for Alzheimer’s disease diagnostics, addressing the practical and accessibility challenges of cerebrospinal fluid sampling and neuroimaging. Technological advances in mass spectrometry and ultrasensitive immunoassays now permit precise quantification of amyloid-β peptides, phosphorylated tau isoforms and neurofilament light chain in peripheral blood. These measurements correlate strongly with in vivo assessments of amyloid plaque deposition, tau aggregation and neuronal injury, supporting their integration into clinical workflows. Beyond case identification, plasma assays enable longitudinal monitoring of disease progression and treatment response, thereby facilitating earlier intervention and more equitable global access to precision neurology.

Research from Nature Portfolio

Recent studies have demonstrated that a mass-spectrometry–based assay for plasma phosphorylated tau217 achieves diagnostic accuracy equivalent to or exceeding that of approved cerebrospinal fluid tests for amyloid and tau pathologies in individuals with mild cognitive impairment and early dementia. Complementary consensus recommendations propose that blood assays for amyloid-β should attain sensitivity of ≥90% and specificity of ≥85% for triaging in primary care, with equivalence to cerebrospinal fluid benchmarks for standalone confirmation. In diverse populations, combined measurements of plasma Aβ42, p-tau181 and neurofilament light chain have discriminated preclinical Alzheimer’s disease from controls up to eight years before symptom onset, underscoring the utility of blood tests for early detection and screening programmes.

Plasma Biomarker Applications in Alzheimer's Disease Diagnostics publication trend

The graph below shows the total number of articles in plasma biomarker applications in alzheimer's disease diagnostics across all publications each year (not limited to Nature Index journals).

Technical terms

Amyloid-β (Aβ42/Aβ40 ratio): The relative concentrations of the 42- and 40-amino-acid variants of amyloid-β peptides, indicative of cerebral amyloid plaque burden.

Phosphorylated tau (p-tau): Tau protein modified by phosphate groups at specific sites (for example, threonine-181, threonine-217 or threonine-231), reflecting tau aggregation in Alzheimer’s pathology.

Neurofilament light chain (NfL): A neuronal cytoskeletal protein released into blood following axonal injury, serving as a marker of neurodegeneration.

Positron emission tomography (PET): A functional neuroimaging technique using radiotracers to visualise amyloid-β plaques, tau tangles or metabolic changes in the brain.

References

1. Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests. Nature Medicine (2024).
2. Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease. Nature Reviews Neurology (2024).
3. Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications. Molecular Neurodegeneration (2023).
4. Plasma biomarkers predict Alzheimer’s disease before clinical onset in Chinese cohorts. Nature Communications (2023).
5. Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints. Translational Neurodegeneration (2023).