title: Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue.
abstract: Aggregation of Aβ amyloid fibrils into plaques in the brain is a universal hallmark of Alzheimer's Disease (AD), but whether plaques in different individuals are equivalent is unknown. One possibility is that amyloid fibrils exhibit different structures and different structures may contribute differentially to disease, either within an individual brain or between individuals. However, the occurrence and distribution of structural polymorphisms of amyloid in human brain is poorly documented. Here we use X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid. Our observations indicate that (i) tissue derived from subjects with different clinical histories may contain different ensembles of fibrillar structures; (ii) plaques harboring distinct amyloid structures can coexist within a single tissue section and (iii) within individual plaques there is a gradient of fibrillar structure from core to margins. These observations have immediate implications for existing theories on the inception and progression of AD.
authors.affiliation: Department of Bioengineering, Northeastern University, Boston, MA, USA.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Costantino
authors.affiliation: GM/CA@APS, Argonne National Laboratory, Illnois 60439, USA.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Venugopalan
authors.affiliation: GM/CA@APS, Argonne National Laboratory, Illnois 60439, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Fischetti
authors.affiliation: Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.affiliation: Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.affiliation: Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez-Isla
authors.affiliation: Department of Bioengineering, Northeastern University, Boston, MA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Makowski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments