Hypothesis: microtubules, a key to Alzheimer disease

Alzheimer disease (AD) is a clinicopathologic syndrome of unknown etiology with numerous abnormalities in neuronal and nonneuronal cells. A review of the literature suggests that a common basic intracellular defect may underlie many of the reported abnormalities. We hypothesize impairment of the microtubule (MT) system as one explanation for the pathogenesis of AD. Evidence in support of the hypothesis includes the following: MTs are ubiquitous and vital cell components, unequally distributed, with the highest concentration in the brain; various abnormalities, including the key neuropathologic lesions, can be explained by impairments of the MT system; and experiments utilizing pharmacologic agents known to disrupt MTs have reproduced certain abnormalities observed in AD. The hypothesis provides a framework for systematic investigations of MTs at the cellular and molecular levels as well as the basis for in vivo diagnostic tests for AD.