Biomarkers are a useful tool for early diagnosis in neurodegenerative diseases such as Alzheimer’s disease (AD). Blood and cerebrospinal fluid (CSF) are some of the most studied tissues for diagnosis. However, diagnostic tools based on validated biomarkers that allow us to diagnose the disease before the first signs of cognitive impairment, are still lacking.
CSF samples from AD patients have shown elevated levels of different proteins such as tau and GFAP compared to controls. These findings suggest a role for not only tau but also for astrocytes in the pathology of the disease.
Here we present liquid Tau Proximity Ligation Assay (l-Tau-PLA) as a promising technique for biomarker detection in fluid tissues. We have established a new protocol of PLA for tau aggregate detection in CSF, allowing us to discriminate between control and late-AD patient samples. In addition, we have characterized the aggregates present in these samples with transmission electron microscopy finding differences not only in their levels but also in their conformation. Furthermore, we have explored the relationship between tau and astrocytes in transgenic mice models of Alzheimer’s and Parkinson’s disease observing differences in tau oligomer content and GFAP intensity among groups. Collectively, these results suggest that l-Tau-PLA is a promising technique for biomarker detection in Alzheimer’s disease, and that astrocytes and tau are closely related in the pathology of the disease.