Identifying Alzheimer's disease genes in apolipoprotein E−/− mice brains with confirmed Porphyromonas gingivalis entry

TL;DR

This study identifies specific genes affected in a mouse model of Alzheimer's disease after infection with a bacteria linked to the condition.

Contribution

The study reveals specific gene expression changes in an Alzheimer's mouse model following Porphyromonas gingivalis infection.

Findings

Five genes showed significant expression changes in ApoE−/− mice brains after P. gingivalis infection.

Cdk5r1 and IL1a were significantly altered at 12 weeks, while Chrna7, Mapk1, and Vnsl1 were altered at 24 weeks.

Most AD target genes showed no difference between infected and sham mice brains.

Abstract

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.

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