A Blood-Based Window Into Alzheimer's
Diagnosing and predicting the onset of neurodegenerative disease is a challenge researchers continue to unravel. While assessments of cognition and behavior allow physicians to diagnose neurodegenerative disease when symptoms are present, researchers are keen on finding a molecular marker that will allow for more precise and earlier detection of disease. As mechanisms for disease are being uncovered, biomarkers for neurodegenerative disease are uncovered likewise. For Alzheimer’s disease (AD), one such case is phosphorylation on the protein tau at Thr181.
As a highly regulated, adaptive protein, tau becomes phosphorylated at over 80 sites for modulation of its microtubule binding activity. Models of neurodegenerative disease have pointed towards hyperphosphorylation of tau as one of the leading drivers of molecular dysfunction in many different diseases, including AD and frontotemporal lobe dementia (FTLD). One of the challenges that remains is matching specific phosphorylation sites on tau to distinct mechanisms and biological outcomes. As AD and FTLD can have similar symptoms in specific cases, they also have similar molecular bases for disease [link out to FTLD vs AD blog post]. This is why pThr181 on tau has become such an important marker for AD.
Medical researchers have conducted longitudinal studies monitoring clinical samples to seek disease markers that can transform how we detect and strategize against disease. Though not much is known about pThr181 mechanistically, it was found in 2020 that elevated phosphorylation at this site, as measured in blood plasma, correlated with the incidence of AD. Why is this so groundbreaking? Monitoring elevated phosphorylation in cerebrospinal fluid (CSF) has historically been helpful for uncovering clues to AD progression, but accessing CSF is highly invasive, unlike blood plasma.
Even more, researchers have found evidence of a relationship between pThr181 and the formation of Aβ plaques, which are characteristic of AD. Though the mechanism of this relationship is not yet completely understood, elevated plasma levels of pThr181 appear highly related to the instance of Aβ plaques. Thus, this site is suitable for distinguishing AD from FTLD and other tauopathies, which may exhibit increased tau phosphorylation but are remarked by the absence of Aβ plaques. In some cases, the cognitive and behavioral symptoms of AD and FTLD can be similar during early stages of disease, so having a molecular indicator allows for researchers and physicians alike to distinguish the two diseases.
Beyond distinction between AD and FTLD, pThr181 may provide a way to predict AD progression. Longitudinal studies of elevated blood plasma pThr181 were able to predict the onset of dementia in patients. Though much more work is necessary to hone in on exactly what is happening on a mechanistic level and better understand how to use pThr181 as a diagnostic tool, discovery of this biomarker offers a foothold for molecular biology studies into the complex web of tau phosphorylation.
Measuring tau phosphorylation becomes challenging without specific tools. Assays like western blotting and immunohistochemistry may seem simple, yet their broad utility has found wide application in neurodegeneration research. As the mechanistic role of sites like pThr181 requires biochemical and molecular biology assays to discover exactly what is being perturbed within the cell, these common assays become consequential to defining the cellular pathology that translates into disease treatment.
Fortunately, HUABIO’s catalog offers antibodies raised against 11 unique tau phospho-sites, including two highly validated clones against pThr181. Don't let nonspecificity prevent your next breakthrough.
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