Alzheimer’s disease (AD) is one of the most prevalent severe neurological disorders afflicting our aged population. Cognitive decline, a major symptom exhibited by AD patients, is associated with neuritic dystrophy, a degenerative growth state of neurites. The molecular mechanisms governing neuritic dystrophy remain unclear. Mounting evidence indicates that the AD-causative agent, β-amyloid protein (Aβ), induces neuritic dystrophy. Indeed, neuritic dystrophy is commonly found decorating Aβ-rich amyloid plaques (APs) in the AD brain. Furthermore, disruption and degeneration of the neuronal microtubule system in neurons forming dystrophic neurites may occur as a consequence of Aβ-mediated downstream signaling. This review defines potential molecular pathways, which may be modulated subsequent to Aβ-dependent interactions with the neuronal membrane as a consequence of increasing amyloid burden in the brain. 1. Introduction Several neurodegenerative disorders share common characteristics including aggregation of misfolded mutant proteins in neurons leading to their deafferentation or loss with resultant structural or functional deficits in specific regions of the central nervous system (CNS) [1]. The most prevalent symptoms of age-related neurodegenerative disease are cognitive decline and movement disorders, along with brainstem and cerebellar signs. Such age-dependent disorders include Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), and Spinal Cerebellar Ataxias (SCAs) [1]. There exists complexity in identifying fundamental molecular mechanisms precipitating neurodegeneration in these age-related brain diseases. However, common molecular signalling pathways have been defined in the specific neuronal populations associated with pathology [2]. Although the initiators of neuronal dysfunction may differ for each neurodegenerative disorder, there may be common molecular pathways which when being dysregulated, drive and exacerbate neurodegeneration. For example, the degeneration seen in AD is a result of amyloid plaques and phosphorylated tau deposition in the cerebral cortex and specific subcortical regions, leading to degeneration in the temporal lobe and parietal lobe, along with parts of the frontal cortex and cingulate gyrus [2]. AD also displays dysregulation in kinase and phosphatase mechanisms along with microtubule motor proteins during the degeneration phase [3, 4]. Therefore, a major question that remains unresolved is whether the dysregulation in specific kinases/phosphatases and vesicular transport mechanisms are
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