Molecular architecture of A beta fibrils grown in cerebrospinal fluid solution and in a cell culture model of A beta plaque formation

作者：Garvey Megan; Baumann Monika; Wulff Melanie; Kumar Senthil T; Markx Daniel; Morgado Isabel; Knuepfer Uwe; Horn Uwe; Mawrin Christian; Faendrich Marcus; Balbach Jochen^*

来源：Amyloid-Journal of Protein Folding Disorders, 2016, 23(2): 76-85.

DOI：10.3109/13506129.2016.1146989

• Alzheimer's disease
• amyloid fibrils
• H/D-exchange
• neurodegeneration
• NMR

Objectives: The detailed structure of brain-derived A beta amyloid fibrils is unknown. To approach this issue, we investigate the molecular architecture of A beta(1-40) fibrils grown in either human cerebrospinal fluid solution, in chemically simple phosphate buffer in vitro or extracted from a cell culture model of A beta amyloid plaque formation.
Methods: We have used hydrogen-deuterium exchange (HX) combined with nuclear magnetic resonance, transmission electron microscopy, seeding experiments both in vitro and in cell culture as well as several other spectroscopic measurements to compare the morphology and residue-specific conformation of these different A beta fibrils.
Results and conclusions: Our data reveal that, despite considerable variations in morphology, the spectroscopic properties and the pattern of slowly exchanging backbone amides are closely similar in the fibrils investigated. This finding implies that a fundamentally conserved molecular architecture of A beta peptide fold is common to A beta fibrils.

• 出版日期2016-6
• 单位迪肯大学