According to one report, a definitive diagnosis of Alzheimer’s disease (AD) was previously possible only after death, but recent biomarker research has led to the development of imaging and spinal fluid tests for those who are still alive. However, the tests can only monitor severe disease and differentiate advanced Alzheimer’s from related disorders. Researchers have identified a biomarker that could help clinicians diagnose Alzheimer’s disease earlier. The report was published in ACS Chemical Neuroscience (MCI).
When hunting for AD biomarkers, some researchers have turned to the study of subtle changes in a protein called tau. These changes, or post-translational modifications, can make the tau protein more likely to clog, leading to neuron loss and impaired memory. Two such modifications involve the phosphorylation of tau at specific amino acids, resulting in variants called p-tau181 and p-tau217.
These biomarkers have been shown to effectively differentiate AD tissues from those with other neurodegenerative diseases. Because it is helpful to have multiple biomarkers in a clinician’s toolbox, Bin Xu, Jerry Wang, Ling Wu and their colleagues sought additional p-tau biomarkers that could be effective AD diagnostics, or that might capture AD in its early stages. Huh.
Using post-mortem brain tissue from AD patients and non-AD subjects, the researchers identified several p-tau biomarkers selectively associated with tau aggregation. Like p-tau181 and p-tau217, several of these biomarkers differentiate AD tissues from healthy controls. One in particular, p-tau198 also differentiated AD from two other neurodegenerative diseases in which tau is known to clump.
Further experiments showed that p-tau198 was as effective as p-tau181 and p-tau217 in these assays. Importantly, both p-tau 198 and p-tau217 can also differentiate brain tissue from patients with MCI, an early sign of AD, from older subjects without any impairment. According to the researchers, no well-established biomarkers currently exist that can diagnose MCI. Thus, p-tau198 and p-tau217 may help clinicians to intervene early, as new treatments become available, before significant neurological damage occurs.
Furthermore, the researchers say that this method could be used to find tau biomarkers with modifications other than phosphorylation.
The authors acknowledge funding from the Biomarkers in Neurodegenerative Disease Program of the Alzheimer’s Association, Alzheimer’s Research UK, The Michael J. Fox Foundation for Parkinson Research, Weston Brain Institute; Duke Clinical and Translational Science Institute; National Institutes of Health; Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund; Diabetes Action Research and Education Foundation; and the Duke/UNC Alzheimer’s Disease Research Center.