Synaptic Pruning in Alzheimer’s Disease: Role of the Complement System

Abstract

<jats:p>Alz heimer’s disease (AD) continues to threaten aged individuals and health care systems around the world. Human beings have been trying to postpone, reduce, or eliminate the primary risk factor for AD, aging, throughout history. Despite this, there is currently only symptomatic treatment for AD and this treatment is limited to only a handful of FDA approved AD drugs.</jats:p>

Quantification of astrocytic synaptic pruning in mouse hippocampal slices in response to ex vivo Aβ treatment via colocalization analysis with C1q

“…We observed greater degree of % ROI colocalization of both C1q eat-me tag as well as PSD95 inside the astrocytic volume, in the hippocampal slices that were incubated with Aβ 42 peptide as compared to the control. This indicates an increased synaptic pruning activity in the presence of Aβ 42 oligomers which correlates with the previous studies in different Alzheimer’s models ( Sellgren et al., 2019 ; Brucato and Benjamin, 2020 ). The statistical analysis can be performed by common programs such as Graph Pad Prism or SPSS.…”

The biological pathways of Alzheimer disease: a review

“…These processes can be influenced by multiple factors, including OS and inflammation, which were already discussed, and novel processes like epigenetic control [271] .…”

“…Rather, it was demonstrated that the once “supporting” cells types present in SNC have an important role in the regulation of Brain processes, including neurotransmission and microenvironment homeostasis [165] , [166] . As briefly described in Box 2 , Microglia modulate synaptogenesis, synapse tagging and elimination or synaptic pruning, help repair damage from injury and modulate synaptic transmission through cytokines [281] and in particular through complement proteins release [271] , [282] .…”

Synapses, Microglia, and Lipids in Alzheimer’s Disease

“… Linnartz-Gerlach et al (2019) demonstrated that aged TREM2 knock-out mice had lower transcription of C1qa, C1qb, C1qc, C3, and C4b. Thus the reactivation of complement-mediated synaptic pruning is a distinct possibility in AD ( Stephan et al, 2012 ; Heppner et al, 2015 ; Brucato and Benjamin, 2020 ; Gomez-Arboledas et al, 2021 ), a scenario that has been also observed in human mutant APP mice (J20) ( Hong et al, 2016 ). Refer to Figure 3 which presents a basic mechanism linking LDAM and aberrant synaptic elimination by microglia which may be mediated by increased complement deposition.…”