Neuronal expression of vimentin in the Alzheimer's disease brain may be part of a generalized dendritic damage-response mechanism.
Early pathological features of Alzheimer's disease (AD) include synaptic loss and dendrite retraction, prior to neuronal loss. How neurons respond to this evolving AD pathology remains elusive. In the present study, we used single- and double-label immunohistochemistry to investigate the relationship between neuronal vimentin expression and local brain pathology. Vimentin was localized to neuronal perikarya and dendrites in AD brain, with vimentin-immunopositive neurons prevalent in regions exhibiting intra- and extracellular beta-amyloid(1-42) (Abeta42) deposition. Neuronal co-localization of vimentin and Abeta42 was common in the cerebral cortex, cerebellum and hippocampus. Additionally, neurons in affected brain regions of AD transgenic (Tg2576) mice and in brain tissue subjected to mechanical injury expressed vimentin, while those in comparable regions of control mouse brain did not. Finally, we show that neurons in human fetal brain express vimentin concurrently with periods of rapid neurite extension. Overall, our results suggest that neurons express vimentin as part of an evolutionarily conserved, damage-response mechanism which recapitulates a developmental program used by differentiating neurons to establish dendrites and synaptic connections.
Levin
Eli C
EC
University of Medicine and Dentistry of New Jersey/Graduate School of Biomedical Sciences, 2 Medical Center Drive, Stratford, NJ 08084, USA.
Acharya
Nimish K
NK
Sedeyn
Jonathan C
JC
Venkataraman
Venkateswar
V
D'Andrea
Michael R
MR
Wang
Hoau-Yan
HY
Nagele
Robert G
RG
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D003712:Dendrites / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D014746:Vimentin