This study by Fitz et al. nicely shows how different ApoE phenotypes may affect amyloid and Aβ levels in the brains of elderly and AD patients.
Here, they highlight a direct correlation of human ApoE4 expression and mouse ABCA1 function as a prerequisite for higher cerebral amyloid levels and behavioral abrogation. The investigations show that the effects are controlled by hApoE4 but not by hApoE3. More interestingly, the effect is exacerbated when the mice partially lack mABCA1 expression (heterozygote condition). Whether the genomic heterozygosity also affects mABCA1 kinetics in the animals was unfortunately not shown. Also, compensational mechanisms, for example, upregulation of other ABCA family members would be of interest for investigations. Additionally, one may ask whether there is also any role for LRP1/RAGE or other ABC transporter family members in this effect.
Nevertheless, the work nicely confirms the functional links between serum
proteins and cerebral ABC transporters. This large superfamily of proteins
recently came into focus in AD research when it was shown...