Can tau filaments be both physiologically beneficial and toxic?

Alzheimer's disease (AD) is a progressive disease of aging primarily characterized at the behavioral level by symptoms of memory loss. The pathological hallmarks of AD are extracellular plaques and intracellular neurofibrillary tangles that are composed of filamentous polymers of beta-amyloid (Abeta) and tau, respectively. Aggregates of filaments are not unique to AD--fibrous polymers are the pathological signatures of many diseases of aging such as Huntington's disease and Parkinson's disease. Whether Abeta or tau filaments cause AD is still an open question, as a wide variety of proteins and pathways have been implicated in the initiation and advancement of the disease--processes such as apoptosis, oxidative stress, and protein degradation. That polymers are the prevalent species observed in aging disorders suggests that this morphology of aggregation represents a significant physiological role. As a consequence of an independent insult or aging itself, the filament shifts from a physiological role to one with pathological implications. The relative importance of Abeta filaments versus tau filaments has also been a focus of significant debate within the research community. Although genetic evidence indicates that Abeta filaments are an integral component in AD, only tau pathology has been found to correlate with symptom presentation in patients. Not only do tau filaments greatly contribute to the systematic loss of neurons and the pathological presentation of memory loss, but they may represent a physiological process whose regulation may be controlled.