α-Internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the β-amyloid plaques in inducing neuronal injury

Abstract

This study investigated the role of α-internexin in the neuronal alterations associated with β-amyloid plaque formation in Alzheimer's disease (AD). Cortical neurons could be defined by their variable content of neurofilament (NF) triplet and α-internexin proteins, with a distinct population of supragranular pyramidal cells containing α-internexin alone. Both NF triplet and α-internexin were localized to reactive axonal structures in physically damaged neurons in experimental trauma models. Similarly, NF triplet and α-internexin immunoreactive neurites were localized to plaques densely packed with β-amyloid fibrils in preclinical AD cases, indicating that certain plaques may cause structural injury or impediment of local axonal transport. However, α-internexin, and not NF triplet, ring-like reactive neurites were present in end-stage AD cases, indicating the relatively late involvement of neurons that selectively contain α-internexin. These results implicate the expression of specific intermediate filament proteins in a distinct hierarchy of differential neuronal vulnerability to AD.

Keywords

• Alzheimer's disease
• Neuronal trauma
• Neurofilament triplet proteins
• α-Internexin
• Neuronal injury
• β-Amyloid plaque