Structural involvement of the glutamatergic presynaptic boutons in a transgenic mouse model expressing early onset amyloid pathology.
While the cholinergic depletion in Alzheimer's disease (AD) has been known for some time, a definitive involvement of other neurotransmitter systems has been somewhat more elusive. Our study demonstrates a clear involvement of both glutamatergic and, to a lesser extent, GABAergic neurons in an early onset transgenic mouse model of AD-like amyloid pathology. Immunohistochemical staining and subsequent quantification has revealed a statistically significant increased density of glutamatergic and GABAergic presynaptic boutons in both the plaque free and plaque adjacent cortical neuropile areas of transgenic mice as compared to non-transgenic controls. Furthermore, amyloid plaque size was shown to have a statistically significant effect on the relative area occupied by dystrophic glutamatergic neurites in the peri-plaque neuropile. These findings support our hypothesis that the amyloid pathology progresses in a time and neurotransmitter specific manner, first in the cholinergic system which appears to be most vulnerable, followed by the glutamatergic presynaptic boutons and finally the somewhat more resilient GABAergic terminals.
Bell
K F S
KF
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, H3G 1Y6, Canada.
de Kort
G J L
GJ
Steggerda
S
S
Shigemoto
R
R
Ribeiro-da-Silva
A
A
Cuello
A C
AC
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000473:pathology*; D019581:Neuropil / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid