Histamine H(1) receptors in patients with Alzheimer's disease assessed by positron emission tomography.
Cerebral histamine H(1) receptor binding was measured in vivo in 11 normal subjects (six young and five old) and 10 patients with Alzheimer's disease by positron emission tomography and [11C]doxepin, a radioligand for H(1) receptors. The parametric images describing the tracer kinetics were generated by either compartmental or graphical analysis, and were examined statistically on region-of-interest and voxel-by-voxel bases. The binding potential of H(1) receptors showed a significant decrease particularly in the frontal and temporal areas of the Alzheimer's disease brain compared to the old, normal subjects. In addition, the receptor binding correlated closely to the severity of Alzheimer's disease assessed by the Mini-Mental State Examination score within several brain areas. The ratio of K1 values between the brain areas and the cerebellum was used as a relative measure of regional cerebral blood flow which decreased in the frontal and temporal areas of the Alzheimer's disease brain. However, the difference in the binding potential (total concentration of receptor/equilibrium dissociation constant) between the Alzheimer's disease patients and the old, normal subjects was greater than that in the cerebral blood flow, and the rate of decrease in the binding potential with the progression of Alzheimer's disease was greater than the rate of decrease in the cerebral blood flow. This study reveals the predominant disruption of the histaminergic neurotransmission in the neurodegenerative processes of Alzheimer's disease. This study suggests that the decline of the histamine receptor binding might play a substantial role in the cognitive deficits of Alzheimer's disease patients.
Higuchi
M
M
Department of Geriatric Medicine, Tohoku University School of Medicine, 980-8574, Sendai, Japan.
Yanai
K
K
Okamura
N
N
Meguro
K
K
Arai
H
H
Itoh
M
M
Iwata
R
R
Ido
T
T
Watanabe
T
T
Sasaki
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002560:Cerebrovascular Circulation; D003071:Cognition; D004316:Doxepin; D005260:Female; D006633:Histamine Antagonists; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011969:Receptors, Histamine H1 / Q000032:analysis*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D004316:Doxepin