Plasma Biomarkers Show Promise in CNS Trials for Alzheimer's Disease
Plasma biomarkers have increasingly been explored in recent years as a non-invasive and cost-effective means of surveying Alzheimer’s disease (AD).
Now, a new study published in Science and Translational Medicine in July 2023 indicates that brain, cerebral spinal fluid (CSF), and plasma proteins are altered in individuals with sporadic AD.
The study reinforces previous findings which indicate that plasma amyloid, tau, and neurodegeneration (ATN) biomarkers show usefulness in cognitively unimpaired (CU) populations for predicting AD onset.
The incidence of AD is characterised by the presence of Aβ plaques and tau tangles; Aβ is specifically thought to potentiate the spread of neocortical tau pathology.
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Recent work on plasma biomarkers has primarily focused on individualised risk assessment in patients with mild cognitive impairment.
However, substantial neuronal loss is typically seen by this stage, lessening the utility of disease modifying therapies intended to slow or prevent dementia onset.
As such, there has been significant interest in the use of plasma biomarkers for predicting longitudinal cognitive decline and clinical outcomes in a CU population of both cognitively normal (CN) health controls and patients with subjective cognitive decline.
This approach could help to identify members of the population at risk from AD and other cognitive diseases who are presently asymptomatic, allowing for the administration of treatment at the earliest stages of disease onset.
Utilising Plasma Biomarkers for AD Prediction
A related study on plasma biomarkers in AD, published in Nature in 2022, hypothesised that a combination of ATN plasma biomarkers could improve the prediction of cognitive decline and clinical outcomes in a CU population.
The study states that further work is needed to validate an optimal panel of biomarkers in an elderly CU population, but their preliminary results suggest that all three core plasma biomarkers could be useful in predicting AD onset.
Less invasive and more affordable blood-based biomarker testing will likely play an important role in selecting individuals for specified biomarker testing.
As more plasma biomarkers complete the validation process, it is hoped that they will become a routine tool in AD diagnosis and clinical trial use.
The accumulation of information will help to provide a more detailed illustration of the type of dementia a patient has by allowing healthcare providers to look for cognitive decline symptoms.
This may also suggest diagnostic performance, helping to predict disease progression with a greater level of accuracy, specificity, and sensitivity.
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Cullen, N.C., Leuzy, A., Janelidze, S. et al. Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations. Nat Commun 12, 3555 (2021). doi: 10.1038/s41467-021-23746-0.
Sung, Y.J. et al. (2023) ‘Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic alzheimer’s disease’, Science Translational Medicine, 15(703). doi:10.1126/scitranslmed.abq5923.
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