Social and Behavioral Sciences Commons^™

Transition From An M1 To A Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition In App/Ps1 Transgenic Mice, Erica M. Weekman, Tiffany L. Sudduth, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Holly M. Brothers, Kaitlyn Braun, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer's disease, yet the impact of these phenotypes on amyloid-beta (Aβ) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Aβ, but long-term studies have not been performed that track the neuroinflammatory phenotype.

METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFNγ or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNγ protein levels and …

Soluble Apoe/Aβ Complex: Mechanism And Therapeutic Target For Apoe4-Induced Ad Risk, Leon M. Tai, Shipra Mehra, Varsha Shete, Steven Estus, G. William Rebeck, Guojun Bu, Mary Jo Ladu

Sanders-Brown Center on Aging Faculty Publications

The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer's disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we …