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bioRxiv · 10.1101/868273

In situ SAXS of protein deposits in Alzheimer's disease

Makowski, L.·Roig Solvas, B.·Hyman, B. T.
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Abstract

Deposits of A{beta} peptides (plaques) and tau protein (neurofibrillary tangles (NFTs)) are ubiquitous features of brain tissue in Alzheimers disease. Their contribution to disease etiology remains controversial. The molecular-to-nano-scale organization of fibrillar species in these protein aggregates remains uncertain, but may contain clues as to the contributions of these structures to disease. Whether or not all plaques are the same structure, and all tangles are the same, has implications for current hypotheses about polymorphic templated misfolding of their constituent proteins, A{beta} and tau. Here we use x-ray microdiffraction in the small-angle regime (SAXS) to probe the molecular organization of these deposits. Using unstained histological sections of human brain tissue, we demonstrate that SAXS can characterize A{beta} fibrils and tau filaments in situ. A{beta} fibrils have a cross-sectional radius of gyration (Rxc) of ~45 [A], and larger (Rxc >150 [A]) aggregates appear to represent A{beta} fibrils that have coalesced side-to-side with one another to create fibrillar bundles or macrofibrillar aggregates. Tau fibrils exhibit an Rxc of ~55 [A] with little sign of coalescence into larger structure. The in situ mapping of these structures revealed subtle variation in A{beta} structure across different brain areas and different cases.

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Makowski, L., Roig Solvas, B., Hyman, B. T.. 2019-12-06. In situ SAXS of protein deposits in Alzheimer's disease. https://doi.org/10.1101/868273

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