Identifying Alzheimer's disease genes in apolipoprotein E^-/- mice brains with confirmed Porphyromonas gingivalis...

The apolipoprotein E allele ε4 is the most well-known predisposing genetic risk factor for Alzheimer's disease (AD).

To identify AD genes in apolipoprotein E^-/- (ApoE^-/-) mice brains with confirmed entry of Porphyromonas gingivalis.

TaqMan™ Mouse AD arrays were performed on orally infected ApoE^-/- mice with confirmed P. gingivalis entry and compared with sham infected mice brains (N = 4) at 12- and 24-weeks post infection.

Gene expression by qPCR demonstrated that in the P. gingivalis 12-weeks post oral infection, two genes were statistically significantly changed in their expression. These were cyclin dependent kinase 5 regulatory subunit 1 (Cdk5r1, 0.15 logfold change, p = 0.05) and Interleukin 1 alpha, (IL1a, -0.10 log fold change, p = 0.012). In the P. gingivalis 24-weeks post oral infection, three genes were statistically significantly changed in their expression. These were cholinergic receptor nicotinic alpha 7 subunit or Chrna7 (0.10 log fold change, p = 0.02), mitogen-activated protein kinase 1 or Mapk1 (0.10 log fold change, p = 0.05) and visinin like 1 or Vnsl1 (0.01 log fold change, p = 0.04). 87 out of 92 AD target genes demonstrated no difference between infected and sham mice brains.

Five genes, from a recognized AD panel had statistically significantly altered expression in the ApoE^-/- mouse AD model following P. gingivalis entry into the brain. This suggests the ApoE^-/- genetic variation may control the biological activity of specific genes relevant to inflammation and neuronal plasticity following P. gingivalis infection.