Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment.

ABSTRACT: The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer's Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer's Disease-like brain pathology as observed by ¹¹C-PiB PET and ¹⁸F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selecti

SUBMITTER: Juul-Madsen K 

PROVIDER: S-EPMC10858199 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature