*4.3. Impact of ABCA7 Depletion in Aβ Burden in Animals and Cells*

When KO animals are crossbred with transgenic mice overproducing Aβ peptides (J20 mice at ± 17 months of age), Aβ burden was worsened, reinforcing the link between ABCA7 and AD. Interestingly, this effect is rather the consequence of a higher Aβ peptide accumulation than an overproduction [86]. Indeed, a significant decrease of Aβ peptide efflux across the BBB was reported in an *Abca7*-deficient in vitro model of the BBB, in relation to ApoA-I lipidation status [20], as well as a decrease in the phagocytosis process mediated by microglial cells [81,86]. These cells express high levels of ABCA7 when compared with neurons [82]. In addition, it was reported that *Abca7* haplodeficiency provokes a microglial abnormal morphology and an altered response to inflammation, thus leading to cerebral amyloid accumulation in mice [87].

On the contrary to the aforementioned study demonstrating that *Abca7* deficiency does not impact Aβ peptide synthesis [86], other studies reported that the absence of *Abca7* in AD transgenic mouse models (APP/PS1 and TgCRND8) promotes the Aβ peptide production [22,83] or that ABCA7 upregulation in vitro diminishes this synthesis [82]. Transgenic models used to reproduce AD in mice should be taken into account and probably explain why such discrepancies are observed. It is important to note that in AD mouse models, ABCA1 and ABCA7 expressions seem to act in the same direction in order to modulate Aβ peptide production and deposition.
