Intermediate Antiparallel β Structure in Amyloid β Plaques Revealed by Infrared Spectroscopic Imaging

Brooke Holcombe, Abigail Foes, Siddhartha Banerjee, Kevin Yeh, Shih Hsiu J. Wang, Rohit Bhargava, Ayanjeet Ghosh

Research output: Contribution to journalArticlepeer-review

Abstract

Aggregation of amyloid β (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 the AD brain. We further validate results with IR imaging of in vitro aggregates and show that the antiparallel β-sheet structure is a distinct structural facet of amyloid fibrils.

Original languageEnglish (US)
Pages (from-to)3794-3803
Number of pages10
JournalACS Chemical Neuroscience
Volume14
Issue number20
DOIs
StatePublished - Oct 18 2023

Keywords

  • Alzheimer’s disease
  • amyloid plaque
  • amyloid β
  • antiparallel β sheets
  • infrared imaging

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Biochemistry
  • Physiology
  • Cell Biology

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