| First Author | Henjum K | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 10590 |
| PubMed ID | 32601313 | Mgi Jnum | J:296369 |
| Mgi Id | MGI:6451955 | Doi | 10.1038/s41598-020-67419-2 |
| Citation | Henjum K, et al. (2020) Analyzing microglial-associated Abeta in Alzheimer's disease transgenic mice with a novel mid-domain Abeta-antibody. Sci Rep 10(1):10590 |
| abstractText | The mechanisms of amyloid-beta (Abeta)-degradation and clearance in Alzheimer's disease (AD) pathogenesis have been relatively little studied. Short Abeta-fragments form by enzymatic cleavage and alternate amyloid-beta precursor protein (APP)-processing. Here we characterized a novel polyclonal Abeta-antibody raised against an Abeta mid-domain and used it to investigate microglial Abeta-uptake in situ by microscopy at the light- and ultrastructural levels. The rabbit Abeta-mid-domain antibody (ab338), raised against the mid-domain amino acids 21-34 (Abeta21-34), was characterized with biochemical and histological techniques. To identify the epitope in Abeta recognized by ab338, solid phase and solution binding data were compared with peptide folding scores as calculated with the Tango software. The ab338 antibody displayed high average affinity (KD: 6.2 x 10(-10) M) and showed preference for C-terminal truncated Abeta-peptides ending at amino acid 34 and Abeta-mid domain peptides with high scores of beta-turn structure. In transgenic APP-mouse brain, ab338 labelled amyloid plaques and detected Abeta-fragments in microglia at the ultra- and light microscopic levels. This reinforces a role of microglia/macrophages in Abeta-clearance in vivo. The ab338 antibody might be a valuable tool to study Abeta-clearance by microglial uptake and Abeta-mid-domain peptides generated by enzymatic degradation and alternate production. |
