Neuroinflammation is involved in the pathology of
Alzheimer's disease (AD). Our major focus was to clarify whether
neuroinflammation plays an important role in AD pathogenesis, particularly prior to the manifestation of overt
dementia. We analyzed
cytokine expression profiles of the brain, with focus on non-demented patients with increasing AD pathology, referred to as high pathology control (HPC) patients, who provide an intermediate subset between AD and normal control subjects, referred to as low pathology control (LPC) patients. With real-time PCR techniques, we found significant differences in
interleukin (IL)-1β, 10, 13, 18, and 33,
tumor necrosis factor-α (TNFα) converting
enzyme (TACE), and
transforming growth factor β1 (TGFβ1)
mRNA expression ratios between HPC and AD patients, while no significant differences in the expression ratios of any
cytokine tested here were observed between LPC and HPC patients. The
cytokine mRNA expression ratios were determined as follows: first,
cytokine mRNA levels were normalized to
mRNA levels of a housekeeping gene, peptidyl-
prolyl isomerase A (PPIA), which showed the most stable expression among ten housekeeping genes tested here; then, the normalized data of
cytokine levels in the temporal cortex were divided by those in the cerebellum, which is resistant to AD pathology. Subsequently, the expression ratios of the temporal cortex to cerebellum were compared among LPC, HPC, and AD patient groups. Our results indicate that
cytokines are more mobilized and implicated in the later AD stage when a significant
cognitive decline occurs and develops than in the developmental course of AD pathology prior to the manifestation of overt
dementia.