Transport of cargo from periphery to brain by circulating monocytes

摘要: The misfolding and aggregation of the Aβ peptide - a fundamental event in pathogenesis Alzheimer׳s disease can be instigated brains experimental animals by intracranial infusion brain extracts that are rich aggregated Aβ. Recent experiments have found peripheral (intraperitoneal) injection seeds induces deposition APP-transgenic mice, largely form cerebral amyloid angiopathy. Macrophage-type cells normally involved pathogen neutralization antigen presentation, but under some circumstances, circulating monocytes been to act as vectors for transport pathogenic agents such viruses prions. present study assessed ability aggregates from peritoneal cavity brain. Our initial showed intravenously delivered macrophages had previously ingested fluorescent nanobeads tracers migrate primarily organs spleen liver, small number also reach parenchyma. We next injected CD45.1-expressing donor mice into CD45.2-expressing host mice; after 24h, analysis fluorescence-activated cell sorting (FACS) histology confirmed CD45.1 enter brain, particularly superficial cortex around blood vessels. When first exposed Aβ-rich human AD cases, subset Aβ-containing These indicate that, mouse models, potential which exogenously delivered, travels periphery more generally support hypothesis macrophage-type participate dissemination proteopathic seeds.