Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment.
We determined whether oxidative stress is an early event in the pathogenesis of sporadic Alzheimer disease (AD), and correlated oxidative stress with neuropsychological functions and neurofibrillary pathology in AD and mild cognitive impairment (MCI). Oxidative stress was measured as the percentage of astrocytes expressing heme oxygenase-1 (HO-1) in post mortem temporal cortex and hippocampus after dual HO-1/glial fibrillary acidic protein (GFAP) immunohistochemistry. Glial HO-1 expression in the MCI temporal cortex and hippocampus was significantly greater than in the non-demented group and did not differ from AD values. Astroglial HO-1 expression in the temporal cortex was associated with decreased scores for global cognition, episodic memory, semantic memory and working memory. Hippocampal astroglial HO-1 expression was associated with lower scores for global cognition, semantic memory and perceptual speed. Glial HO-1 immunoreactivity in the temporal cortex, but not hippocampus, correlated with the burden of neurofibrillary pathology. Cortical and hippocampal oxidative stress is a very early event in the pathogenesis of sporadic AD and correlates with the development of specific cognitive deficits in this condition.
Schipper
Hyman M
HM
Centre for Neurotranslational Research and Bloomfield Centre for Research in Aging, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, Que., Canada H3T 1E2. hyman.schipper@mcgill.ca
Bennett
David A
DA
Liberman
Adrienne
A
Bienias
Julia L
JL
Schneider
Julie A
JA
Kelly
Jeremiah
J
Arvanitakis
Zoe
Z
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D003072:Cognition Disorders / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009457:Neuroglia / Q000201:enzymology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011180:Postmortem Changes; D013223:Statistics as Topic
D005904:Glial Fibrillary Acidic Protein; D051547:Heme Oxygenase-1