Old age, environmental factors and mutations in amyloid precursor protein (APP) are all implicated in the development of Alzheimer’s disease (AD). In AD, accumulation of insoluble amyloid (Ab42) and abnormal tau protein phosphorylation leads to the formation of amyloid plaques and neurofibrillary tangles. These pathological hallmarks of AD cause neuronal death and neurotransmitter deficits in areas of the brain associated with higher mental functioning. Expression of the ApoE4 isoform of apolipoprotein, oxidative cell damage and inflammatory changes in the brain are also implicated in AD.
The innate inflammation observed in Alzheimer’s disease (AD) is an endogenously mediated localized action, brought about as a response to tissue injury and the chronic presence of deposits of insoluble, fibrillar Aβ. The cellular mediators of inflammation in the AD brain are astrocytes, neurones and microglia. These cells are capable of activating a number of inflammatory mediators, including cyclooxygenase-2 (COX-2), the complement pathway and pro-inflammatory cytokines such as interleukin1 (IL-1) and tumour necrosis factor α (TNFα). The inflammatory cascade in the AD has long been a therapeutic target for the treatment of AD, with non-steroidal anti-inflammatory drugs (NSAIDs) being of particular interest.