Altered expression of COX-2 in subdivisions of the hippocampus during aging and in Alzheimer's disease: the Hisayama Study.
BACKGROUND
It has been reported that nonsteroidal anti-inflammatory drugs may delay the onset of Alzheimer's disease (AD). Since nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX), COX-2, an inducible form of COX, may be involved in the pathology of AD in association with the arachidonic acid cascade. In addition, it has been suggested that alterations in the balance of polyunsaturated fatty acids are associated with brain dysfunctions such as neurodegerative pathologies of the aging brain.


METHODS
To explore COX-2 expression in the hippocampus, we analyzed 45 consecutive autopsy subjects without dementia and 25 AD patients derived from the town of Hisayama, Japan.


RESULTS
The neuronal expression of COX-2 in the CA3 subdivision of the hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were consistently observed in both nondemented and AD brains, and COX-2 immunoreactivity correlated with age in nondemented brains. In AD patients, neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with the severity of AD pathology. This correlation was not apparent in nondemented subjects.


CONCLUSIONS
These results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction.
Fujimi
Kouhei
K
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. fujimi@np.med.kyushu-u.ac.jp
Noda
Kazuhito
K
Sasaki
Kensuke
K
Wakisaka
Yoshinobu
Y
Tanizaki
Yumihiro
Y
Iida
Mitsuo
M
Kiyohara
Yutaka
Y
Kanba
Shigenobu
S
Iwaki
Toru
T
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D012720:Severity of Illness Index
D051546:Cyclooxygenase 2