Alzheimer’s disease: an aging-related gene expression disorder targeting proteins responsible for neuroplasticity

Alzheimer’s disease causes a progressive loss of memory and cognitive ability in the last decades of life. Clues to what causes these symptoms are suggested by the hallmark Alzheimer’s disease pathologies: amyloid plaques, tau tangles, and degeneration in the basal forebrain cholinergic system. Multiple treatment strategies for Alzheimer’s disease that attempt to remedy or remove these pathologies have met with limited success. We briefly review those strategies and hypothesize that the most effective treatment for Alzheimer’s disease might be gene therapy that replaces down-regulated proteins essential to the neuroplasticity underlying memory. Specifically, we suggest replacing tubulin isotypes that participate in memory-related structural change. This strategy stands to reverse Alzheimer’s disease memory deficits directly. Indirectly, this approach may halt or slow the formation of tau tangles and amyloid plaques. Microtubules lie at the crossroads of memory decline and Alzheimer’s disease pathology. Gene therapy may act as a "magic bullet" by restoring healthy microtubules essential for brain function. The proposed cascade suggests that microtubule disintegration precedes, rather than follows, tau tangle and plaque formation.