alpha-Internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the beta-amyloid plaques in inducing neuronal injury.
This study investigated the role of alpha-internexin in the neuronal alterations associated with beta-amyloid plaque formation in Alzheimer's disease (AD). Cortical neurons could be defined by their variable content of neurofilament (NF) triplet and alpha-internexin proteins, with a distinct population of supragranular pyramidal cells containing alpha-internexin alone. Both NF triplet and alpha-internexin were localized to reactive axonal structures in physically damaged neurons in experimental trauma models. Similarly, NF triplet and alpha-internexin immunoreactive neurites were localized to plaques densely packed with beta-amyloid fibrils in preclinical AD cases, indicating that certain plaques may cause structural injury or impediment of local axonal transport. However, alpha-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 alpha-internexin. These results implicate the expression of specific intermediate filament proteins in a distinct hierarchy of differential neuronal vulnerability to AD.
Dickson
Tracey C
TC
NeuroRepair Group, University of Tasmania, Hobart, Tasmania, 7000, Australia. Tracey.Dickson@utas.edu.au
Chuckowree
Jyoti A
JA
Chuah
Meng Inn
MI
West
Adrian K
AK
Vickers
James C
JC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D015984:Causality; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; C046643:alpha-internexin