RT Journal Article SR Electronic T1 Intermediate antiparallel beta structure in amyloid plaques revealed by infrared spectroscopic imaging JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.04.18.537414 DO 10.1101/2023.04.18.537414 A1 Holcombe, Brooke A1 Foes, Abigail A1 Banerjee, Siddhartha A1 Yeh, Kevin A1 Wang, Shih-Hsiu J. A1 Bhargava, Rohit A1 Ghosh, Ayanjeet YR 2023 UL http://biorxiv.org/content/early/2023/04/20/2023.04.18.537414.abstract AB Aggregation of amyloid beta (Aβ) peptides into extracellular plaques is a hallmark of the molecular pathology of Alzheimer’s disease (AD). Amyloid aggregates have been extensively studied in-vitro, and it is well known that mature amyloid fibrils contain an ordered parallel β structure. The structural evolution from unaggregated peptide to fibrils can be mediated through intermediate structures that deviate significantly from mature fibrils, such as antiparallel β-sheets. However, it is currently unknown if these intermediate structures exist in plaques, which limits the translation of findings from in-vitro structural characterizations of amyloid aggregates to AD. This arises from the inability to extend common structural biology techniques to ex-vivo tissue measurements. Here we report the use of infrared (IR) imaging, wherein we can spatially localize plaques and probe their protein structural distributions with the molecular sensitivity of IR spectroscopy. Analyzing individual plaques in AD tissues, we demonstrate that fibrillar amyloid plaques exhibit antiparallel β-sheet signatures, thus providing a direct connection between in-vitro structures and amyloid aggregates in AD brain. We further validate results with IR imaging of in-vitro aggregates and show that antiparallel β-sheet structure is a distinct structural facet of amyloid fibrils.Competing Interest StatementThe authors have declared no competing interest.