Clinical Information

The two main neuropathologic features observed in the brain of patients with Alzheimer disease (AD) are the presence of plaques composed of beta-amyloid (Abeta) peptides and intracellular neurofibrillary tangles containing hyperphosphorylated Tau (p-Tau) proteins. To date, positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers are the most widely used biomarkers in clinical practice for detection of Abeta and tau pathologies. There are several PET tracers that can detect the load of Abeta fibrils in the brain (amyloid-PET). Studies have demonstrated high concordance between the in vivo uptake of these amyloid-PET tracers and the density of Abeta plaques as determined post-mortem. In CSF, Abeta42 concentrations and especially the ratios of Abeta42/Abeta40 and p-Tau181/Abeta42 concentrations correlate strongly with amyloid-PET status and AD neuropathology. Several CSF Abeta and p-Tau assays on high-performing, fully automated platforms are currently used in clinical practice. However, there is a need for accurate AD blood-based biomarkers that are easily accessible and minimally invasive.

Different p-Tau isoforms that are increased in the presence of amyloid pathology are detectable in plasma, including pTau181, pTau217, and pTau231. Head-to-head comparisons of assays for p-Tau181, p-Tau217, and p-Tau231 using plasma from patients with mild cognitive impairment indicate that increases in plasma p-Tau217 were superior at detecting AD pathology and predicting future development of AD dementia. Both p-Tau181 and p-Tau217 were associated with both Abeta plaques and tau tangles, with p-Tau217 showing stronger correlations with both pathologies. In addition, plasma concentrations of p-Tau217, but not p-Tau181 and p-Tau231, have been shown to increase over time in people with abnormal brain Abeta deposition correlating with brain atrophy and cognitive decline.