Neurobiological role of Alzheimer's disease genetic risk factor ApoE on early synaptic changes in Alzheimer-like models.

• DOI: 10.1002/alz.053484
• Publication Date: 2021-12-01
• Authors: Sabine C. Konings; Emma Nyberg; Isak Martinsson; Gunnar K. Gouras
• Keywords: Apolipoprotein E

The presence of an apolipoprotein E4 (ApoE4) genotype is the major genetic risk factor for Alzheimer's disease (AD). Astrocytes are main source ApoE in brain, however can also be produced by neurons and microglia. plays a role many cell types processes related to AD, however, it remains unclear which mechanism(s) cellular most critical AD. One earliest changes AD early such as endosomal synaptic alterations. ApoE4 has been associated with impaired trafficking dysregulated plasticity. Neuronal hyperexcitability reported mice expressing human ApoE4, dysregulation that seen transgenic mice. Although seems play crucial neuronal linked ApoE's localization mechanisms remain poorly understood. In this study, aim determine ApoE, particular on alterations models.Mouse astrocytes derived from wild-type, knock-out (KO), humanized ApoE3 knock-in Astrocyte-conditioned medium mouse recombinant used treat KO, wild-type APP/PS1 neurons. Additionally, KO treated synthetic Aβ or vehicle control. Analysis performed using immunofluorescence, confocal live imaging.Exogenously added endogenously shown present at neurites terminals cultured Differences activity observed among different conditions Ca2+ microscopy, both absence elevated Aβ. Added endogenous appear endosome-lysosome system neurons.ApoE appears localize synapses endosomes, sites excitability. Determining neurobiology connection vulnerable contribute better understanding