Therapeutic Opportunities in Alzheimer Disease: One for all or all for One?

Michael   W.   Marlatt; Kate   M.   Webber; Paula   I.   Moreira; Hyoung-gon      Lee; Gemma      Casadesus; Kazuhiro      Honda; Xiongwei      Zhu; George      Perry; Mark   A.   Smith

doi:10.2174/0929867053764644

Abstract

In recent years, Alzheimer disease (AD) has received great attention as an incurable and fatal disease that threatens the lives of aging individuals. Debates regarding areas of research and treatment designs have made headlines as scientists in the field question ongoing work. Despite these academic quarrels, significant insights concerning the cellular and molecular basis of AD have illuminated the potential causes and consequences of AD pathogenesis in the human brain. Additionally, assigning relationships among scientific evidence is difficult due to the nature of the disease. It is crucial to note that all findings do not constitute causality as AD has many stages of progression, and therefore a particular finding may reflect disease epiphenomenon. Determining the primary causes of disease are even more problematic when considering that a succinct timeline in which a normal aging brain develops AD-like changes due to a single cause may not be appropriate, as increasing lines of evidence indicate that multiple factors likely contribute to the clinical manifestation of AD. Implications for therapeutic strategies are dramatically affected by viewing AD as a multifactorial disease state, one specific treatment may not be able to prevent or reverse AD if this is indeed the case. In this regard, the current focus on individual therapeutic targets may prove to be ineffective in the successful treatment of AD; however, if taken in combination, these singular therapies may likely result in the global suppression of AD. In this review, the scientific basis for common AD therapeutics as well as the efficacy of these treatments will be discussed.

Keywords: neurodegenerative disease, tau protein, cerebral cortex, dementia, amyloidoses, gene polymorphisms, reactive oxygen species (ros), oxidative stress, bace knockout mice, microglial phagocytosis