Researchers have identified a biomarker that could help physicians diagnose Alzheimer’s disease earlier, as a patient transitions into mild cognitive impairment.
Until recently, a definitive diagnosis of Alzheimer’sAlzheimer's disease is a disease that attacks the brain, causing a decline in mental ability that worsens over time. It is the most common form of dementia and accounts for 60 to 80 percent of dementia cases. There is no current cure for Alzheimer's disease, but there are medications that can help ease the symptoms.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Alzheimer’s disease (AD) was once only possible after someone had died. However, contemporary biomarker studies have led to the development of imaging and spinal fluid tests for those still living. These tests can only monitor severe disease, differentiating advanced AD from related disorders. Scientists have now identified a biomarker that could help physicians diagnose AD earlier, as a patient transitions into mild cognitive impairment (MCI). The findings will be reported today (November 9) in the journal ACS Chemical Neuroscience.
When hunting for AD biomarkers, some researchers have turned to the study of subtle changes in a protein called tau. These changes, or posttranslational modifications, can make the tau protein more likely to clump, which leads to neuron loss and impaired memory.
Two such modifications involve the phosphorylation of tau at specific amino acids<div class="cell text-container large-6 small-order-0 large-order-1">
<div class="text-wrapper"><br />Amino acids are a set of organic compounds used to build proteins. There are about 500 naturally occurring known amino acids, though only 20 appear in the genetic code. Proteins consist of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a shape that is biologically active. The amino acid sequences of proteins are encoded in the genes. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food.<br /></div>
</div>” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>amino acids, resulting in versions called p-tau181 and p-tau217. These biomarkers have been shown to effectively differentiate AD tissues from those of people with other neurodegenerative diseases. Because it’s helpful to have many biomarkers in the physicians’ toolbox, Bin Xu, Jerry Wang, Ling Wu, and colleagues sought additional p-tau biomarkers that could be effective AD diagnostics, or that could perhaps catch AD at its early stages.
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 differentiated AD tissues from healthy controls. One in particular — p-tau198 — also discriminated 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 also could differentiate the brain tissue of patients with MCI — an early sign of AD — from older subjects without the impairment.
According to the researchers, no well-established biomarkers that can diagnose MCI currently exist. Thus, p-tau198 and p-tau217 could help clinicians intervene early, as new treatments become available, before significant neurological damage occurs.
In addition, the researchers say this method could be used to find tau biomarkers with other modifications aside from phosphorylation.
Reference: “Site-specific Phosphor-tau Aggregation-based Biomarker Discovery for AD Diagnosis and Differentiation” 9 November 2022, ACS Chemical Neuroscience.
DOI: 10.1021/acschemneuro.2c00342
The authors acknowledge funding from the Biomarkers Across Neurodegenerative Diseases Program of the Alzheimer’s Association, Alzheimer’s Research UK, The Michael J. Fox Foundation for Parkinson’s Research, the Weston Brain Institute; Duke Clinical & Translational Science Institute; the National Institutes of Health; the 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.
The authors have filed a provisional patent on the work.
Source: SciTechDaily
