biostudies-literatureHenry LSynapsis Foundation-Dementia Research Switzerlan550-564https://www.ebi.ac.uk/biostudies/studies/S-EPMC12879737biostudies-literatureUnknown17(3)Amyloid polymorphism can reflect Alzheimer's disease (AD) stages. This paper demonstrates that amyloid β (Aβ) peptides, primarily Aβ-40 and Aβ-42 (implicated in AD pathology), present in cerebrospinal fluid (CSF), can be differentiated, and their morphology studied in detail using fluorescence-based super-resolution and atomic force microscopy (AFM). An inhibitory effect of Aβ-40 on Aβ-42 protein aggregation, marked by Aβ-40 oligomers colocalizing along the Aβ-42 fibril backbone, was resolved at the single-particle level. Molecular dynamics simulations revealed that coaggregation is modulated by the ionic environment in CSF, where calcium ions form bridges between Glu residues of Aβ-40 and Aβ-42, known to stabilize the fibril structure. This ion-mediated tethering compacts Aβ-40 and kinetiACS chemical neuroscienceDifferentiating Alzheimer's Aβ Isoforms Coaggregated in Cerebrospinal Fluid via Single-Particle Imaging.PMC128797372022-PI03Bhattacharya SHenry LPinotsi DNirmalraj PNBergaglio TfalseDifferentiating Alzheimer's Aβ Isoforms Coaggregated in Cerebrospinal Fluid via Single-Particle Imaging.Amyloid polymorphism can reflect Alzheimer's disease (AD) stages. This paper demonstrates that amyloid β (Aβ) peptides, primarily Aβ-40 and Aβ-42 (implicated in AD pathology), present in cerebrospinal fluid (CSF), can be differentiated, and their morphology studied in detail using fluorescence-based super-resolution and atomic force microscopy (AFM). An inhibitory effect of Aβ-40 on Aβ-42 protein aggregation, marked by Aβ-40 oligomers colocalizing along the Aβ-42 fibril backbone, was resolved at the single-particle level. Molecular dynamics simulations revealed that coaggregation is modulated by the ionic environment in CSF, where calcium ions form bridges between Glu residues of Aβ-40 and Aβ-42, known to stabilize the fibril structure. This ion-mediated tethering compacts Aβ-40 and kineti2026-01-01T00:00:00Z2026 Feb2026-07-15T13:47:55.234Z2026-07-05T03:08:38.181ZS-EPMC128797374153244510.1021/acschemneuro.5c00692