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Quantitative proteomics of detergent insoluble tangles derived from Alzheimer’s disease brains

Ionic detergent N‐laurly sarcosine (Sarkosyl) has been the general choice of extraction and enrichment of detergent‐insoluble protein aggregates from different neurodegenerative proteinopathies from human post‐mortem brains. Sarkosyl‐insoluble pellets from Alzheimer’s disease (AD) brains yield fibrils made up of paired helical filaments (PHFs) and straight helical filaments (SHF) of microtubule associated protein tau (MAPT), component of the neurofibrillary tangles in AD. Recent complementary cryo‐EM images and proteomic analysis have provided structural as well as biochemical detail of the core of these fibrillar elements. However, topographic detail of the PHFs and SHFs are still not complete as sarkosyl‐insoluble pellets are also known to contain amyloid‐beta (Aβ), another key hallmark of AD and warrants further assessment.