Brain inflammation, cholesterol, and glutamate as interconnected participants in the pathology of Alzheimer's disease.
Alzheimer's disease (AD) represents one of the most common ailments afflicting the rapidly growing elderly segment of today's population. Despite the vast amount of effort expended in developing a cure, currently approved drugs address only cognitive symptoms that, although important for improving a patient's daily living standard, do not provide a significant delay or halt to disease progression. Early reports that individuals taking anti-inflammatory medications reduce their risk of developing AD has led to the "inflammation hypothesis" of AD and the subsequent testing of these drugs in the clinic. Tests of a select few of these medications in AD clinical trials have, however, yielded disappointing results. Reports of statin-based medications reducing the risk of AD have also led to the testing of this class of drugs in the clinic. Recently, the approval of the NMDA receptor antagonist memantine (Namenda) has provided clinical support for glutamatergic processes in the disease and generated a renewed interest in the role of excitatory amino acids in the etiology of AD. In this review, we take a closer look at these three compelling areas for addressing AD therapeutics: inflammation, cholesterol, and glutamate. We present arguments that these components are interconnected and mutually regulate processes involved in AD progression. Special focus is given to inflammation as a central feature of AD that may be acting in synergy with cholesterol and glutamate to mediate the observed pathophysiology.
Ringheim
G E
GE
Aventis Pharmaceuticals, Inc., Bridgewater, NJ 08807, USA. garth.ringheim@aventis.com
Szczepanik
A M
AM
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D018450:Disease Progression; D004660:Encephalitis / Q000503:physiopathology*; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
D005971:Glutamates; D002784:Cholesterol