Localization of fibrillar polymorphs in human brain tissue

Fibrillar aggregates of Abeta peptides and tau protein are defining features of Alzheimer's disease (AD) but the role these structures play in the etiology of disease remains uncertain. Outstanding questions remain as to the distribution of polymorphs between and within cases. The proposed work will apply x-ray scanning micro- and nano-diffraction to histological sections of human brain tissue in order to map the distribution and arrangement of fibrillar aggregates of these proteins in plaques and tangles. The central hypothesis of the proposed work is that the spatial distribution of structural polymorphs in brain tissue will provide important clues as to how fibrils contribute to disease. The results of these studies will provide a preliminary assessment of whether or not different fibrillar polymorphs spread by a prion-like process during disease progression and provide insights into the mechanisms by which different strains are associated with different disease subtypes.