Alzheimer's disease and inflammation: A review of cellular and therapeuticmechanisms

1. Of the neurodegenerative diseases that cause dementia, Alzheimer's disea se (AD) is the most common. Three major pathologies characterize the diseas e: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments th ought to target this pathology. 2. The senile plaques of AD consist primarily of complexes of the beta-amyl oid protein. This protein is central to the pathogenesis of the disease. 3. Inflammatory microglia are consistently associated with senile plaques i n AD, although the classic inflammatory response (immunoglobulin and leucoc yte infiltration) is absent. beta-Amyloid fragments appear to mediate such inflammatory mechanisms by activating the complement pathway in a similar f ashion to immunoglobulin. 4. Epidemiological studies have identified a reduced risk of AD in patients with arthritis and in leprosy patients treated with anti-inflammatory drug s. Longitudinal studies have shown that the consumption of anti-inflammator y medications reduces the risk of AD only in younger patients (< 75 years). 5. There is a considerable body of in vitro evidence indicating that the in flammatory response of microglial cells is reduced by non-steroidal anti-in flammatory drugs (NSAID). However, no published data are available concerni ng the effects of these medications on brain pathology in AD. 6. Cyclo-oxygenase 2 enzyme is constitutively expressed in neurons and is u p-regulated in degenerative brain regions in AD. Non-steroidal anti-inflamm atory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and increased platelet activation and increased circulating beta-amyloid have been identified in AD, Anti-pl atelet medication (including NSAID) would prevent such activation and its p otentially harmful consequences. 8. Increased levels of luminal beta-amyloid permeabilizes the blood-brain b arrier (BBB) and increases vasoconstriction of arterial vessels, parallelin g the alterations observed with infection and inflammation. Cerebral amyloi dosis is highly prevalent in AD, compromising the BBB and vasoactivity, Ant i-inflammatory medications may alleviate these problems.