Progressive neuronal injury associated with amyloid plaque formation in Alzheimer disease.
Neuronal injury associated with amyloid plaque progression in Alzheimer disease was examined using TUNEL combined with beta-amyloid immunolabeling. There was a progressive increase in the frequency of TUNEL-positive neurons associated with plaque types representing a hypothesized sequence of plaque evolution, from 20% of neurons not associated with plaques to 40%, 70-80%, and 100% of neurons in diffuse, neuritic, and dense-core non-neuritic plaques, respectively. The total number of neurons associated with end-stage, dense-core, non-neuritic plaques declined by 70% (per unit plaque area) compared with neuritic plaque forms. This decline, together with the fact that virtually all of those remaining were TUNEL-positive, suggests that neuronal cell damage increases as plaques evolve from diffuse to more complex forms and that eventually all plaque-associated neurons are lost. This novel demonstration of neurotoxicity associated with amyloid plaque formation and progression suggests that plaque-associated neuronal injury is a major cause of neuronal loss in Alzheimer disease.
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
J G
JG
Sheng
X Q
XQ
Zhou
R E
RE
Mrak
W S
WS
Griffin
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*
D016229:Amyloid beta-Peptides