EMBER multi-dimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains.

, as well as Aβ deposits in different transgenic mouse models. Our imaging method rapidly identifies conformational differences in Aβ and tau deposits from Down syndrome, sporadic and familial Alzheimer's disease human brain slices. We also identified distinct conformational strains of tau inclusions in astrocytes, oligodendrocytes, and neurons from Pick's disease. These findings will facilitate the identification of pathogenic protein aggregates to guide research and treatment of protein misfolding diseases.