AAIC 2021 | Mass spectrometry-based proteomics identifies progressive changes in tau PTMs over time

Judith Steen, PhD, of the Boston Children’s Hospital, Boston, MA, summarizes a study that used mass spectrometry-based proteomics to investigate the distinctive molecular features of tau in patients with Alzheimer’s disease and control subjects. Tau was analyzed from pathological fractions and this data was interfaced with clinical data. It was demonstrated that the molecular features of tau changed progressively throughout the disease course, with the observed post-translational modifications (PTMs) found to be different at different Braak stages and in controls. The addition of these PTMs is ordered, with some modifications only seen early on in Alzheimer’s, whilst others are only seen in the later stages. Some specific PTMs were only seen in the symptomatic group, such as the addition of ubiquitin, and others were only seen in asymptomatic patients that were progressing towards dementia. The presence of these modifications has implications for biomarkers and therapeutics, both of which may need to be investigated in a stage-specific manner. This interview took place during the Alzheimer’s Association International Conference (AAIC) 2021.