Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases?
In less than a decade, beginning with the demonstration by Floyd, Stadtman, Markesbery et al. of increased reactive carbonyls in the brains of patients with Alzheimer's disease (AD), oxidative damage has been established as a feature of the disease. Here, we review the types of oxidative damage seen in AD, sites involved, possible origin, relationship to lesions, and compensatory changes, and we also consider other neurodegenerative diseases where oxidative stress has been implicated. Although much data remain to be collected, the broad spectrum of changes found in AD are only seen, albeit to a lesser extent, in normal aging with other neurodegenerative diseases showing distinct spectrums of change.
Perry
George
G
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Nunomura
Akihiko
A
Hirai
Keisuke
K
Zhu
Xiongwei
X
Pérez
Mar
M
Avila
Jesús
J
Castellani
Rudolph J
RJ
Atwood
Craig S
CS
Aliev
Gjumrakch
G
Sayre
Lawrence M
LM
Takeda
Atsushi
A
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005609:Free Radicals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
D005609:Free Radicals; D017382:Reactive Oxygen Species