Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease

• DOI: 10.1016/j.bbi.2022.10.009
• Publication Date: 2022-10-18T06:45:29Z
• Authors: Mandy S.J. Kater; Christiaan F.M. H...; Takuya Oshima; Niek S. Renckens; Jinte Middeldorp; Erik W.G.M. Boddeke; August B. Smit; Bart J.L. Eggen; Elly M. Hol; Mark H.G. Verheijen
• Keywords: Gliosis; Cognitive Decline

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates early deficits in AD patients are synapse loss gliosis. In particular, it unclear whether activation microglia (microgliosis) has neuroprotective or pathological role AD. Here we report that microgliosis an mediator synaptic dysfunction impairment APP/PS1 mice, mouse model increased amyloidosis. We found appearance microgliosis, behavioral coincided with soluble Aβ42 levels, occurred well before presence Aβ plaques. Inhibition microglial activity treatment minocycline (MC) reduced gliosis, impairments at stages was most effective when provided preventive, i.e., onset microgliosis. Interestingly, levels deposition were not affected preventive MC stage (4 months) whereas these upon later (6 months). conclusion, this study demonstrates importance early-stage prevention on development which might be clinically relevant preventing memory delaying pathogenesis.