A genotype-dependent role for APOE has also been reported in VMCs, including pericytes. VMC-expressed apoE has been shown to differentially regulate neurobehaviors, gliovascular functions, and transcriptomic profiling depending on isoforms [146]. Transcriptomic profiles in human pericytes isolated from the prefrontal cortex and the hippocampus show an upregulation of apoE4 both at the transcript and at the protein levels compared to apoE3 [67]. Similarly, in a human iPSC-derived BBB model, apoE4-expressing VMCs with pericyte-like properties display elevated apoE levels compared to those expressing apoE3, which could be in part responsible for amyloid accumulation in the vasculature. Thus, APOE is differentially regulated depending on the cell-type it is expressed by, supporting the consideration of cell-type specific targeting of apoE [67].
Best Of Fashion Tv Part 42 Model 168
One promising apoE-focused therapeutic avenue is the use of immunotherapies to reduce apoE, in particular apoE4, and consequently alleviate Aβ deposition (Fig. 2). In vivo experiments showed that intraperitoneal injection of HJ6.3, a monoclonal antibody specific against apoE, is effective in reducing amyloid deposition by modulating microglial responses and inflammatory cytokine levels [193]. Administration of HJ6.3 to amyloid model mice reduces Aβ pathology, improves spatial learning performance, and restores functional connectivity without altering plasma cholesterol levels when administered both prior to and after plaque onset [194]. These data demonstrate that reducing apoE4 level may be beneficial in attenuating AD pathology. 2ff7e9595c
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