Alzheimer’s (AD) is a neurological disease which is increasingly affecting the global population. The disease tends to manifest itself years before clinical symptoms occur, this is known as the silent phase and can last two or more decades. During this phase amyloid plaques which are a form of disordered or mis-folded protein aggregates slowly accumulate within the nerve cells of the brain, consequently causing the cognitive impairments seen in AD patients. Despite the heavy research conducted on AD, researchers are still searching for a more affordable method of diagnosis during the pre-clinical phase of AD which would optimistically retard the progression of the disease.
It was previously discovered that individuals with amyloid plaques tend to have certain forms of tau proteins found in their cerebrospinal fluid (Barthelemy, Bateman et al. 2020). These proteins are contained within axons of the nerve cells, they aid in the binding and stabilization of microtubules, and are essential in structures that transport nutrients within nerve cells. This, however, is disrupted in AD as hyperphosphorylated tau proteins form tangles known as neurofibrillary tangles (NFT). Researchers have seen that proteins in the cerebrospinal fluid cross over into the blood and reasoned that sampling blood may indicate whether a person has the proteins associated with AD, hence an exploratory study was conducted to test and evaluate this possibility.
Researchers from The University of Charles F. and The Joanne Knight Alzheimer’s Disease Research Centre analysed blood samples and brain scans from 34 participants. Mass spectrometry was used to identify and measure the different forms of tau within the blood samples. Researchers found that levels of phosphorylated tau 217 (PT217) correlated with the presence of amyloid plaques in the brain. It was also discovered that the individuals with amyloid in their brain had two to three times more PT217 in their blood compared to individuals without amyloid, and that these levels were evident in those with no signs of cognitive decline.
Researchers replicated the analysis using a separate group of 92 people; 42 without amyloid, 20 with amyloid but without cognitive symptoms, and 20 with amyloid and with symptoms. Even in the replicated analysis it was shown that levels of PT217 in the blood correlated with the presence of amyloid in the brain, with more than 90% accuracy. Researchers also observed the blood levels of PT217 in those with no cognitive symptoms and were able to distinguish individuals in the pre-clinical asymptotic stage of AD from healthy people with an 86% accuracy. These findings although exploratory, provide a foundation for a promising early diagnostics test using PT217 as a target.
Source: Barthelemy, N. R., et al. (2020). “Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer’s disease and PET amyloid-positive patient identification.” Alzheimers Res Ther 12(1): 26.