BACKGROUND: Amyloid-β (Aβ) peptides derive from the amyloid precursor protein 
(APP) and play a pivotal role in Alzheimer's disease (AD) pathogenesis. Our 
previous work showed that the APP intracellular domain (AICD), which is produced 
simultaneously with Aβ, also contributes to the development of AD-like features. 
Studies show that administration of apolipoprotein E (apoE) and apoE-derived 
small peptide mimetics protect AD mouse models against these AD-like features. 
However, the effects of apoE-mimetic treatment on AICD-mediated AD-like 
pathologies remain to be elucidated.
OBJECTIVE: To study the effects of an apoE mimetic (COG112) on 
neuroinflammation, hyperphosphorylation of tau and defects in adult neurogenesis 
in AICD- overexpressing transgenic mice (FeCγ25 line).
METHODS: Beginning at 1 month of age, animals were administered subcutaneous 
COG112 3 times per week for 3 months, followed by immunohistochemical analysis 
for neuroinflammation, neurogenesis and phosphorylated tau.
RESULTS: Treatment with COG112 significantly reduced neuroinflammation in AICD 
mice and protected against impaired adult hippocampal neurogenesis. We also 
found that COG112 treatment reduced hyperphosphorylation and somatodendritic 
accumulation of tau in the hippocampus and cerebral cortex of AICD mice.
CONCLUSIONS: Reduction of neuroinflammation by the apoE-mimetic COG112 protects 
against impaired neurogenesis and tau pathology in AICD transgenic mice. These 
data suggest that neuroinflammation plays an important role in AICD-induced 
AD-like pathologies.