Accumulation of 3,4-dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase A metabolite of norepinephrine, in locus ceruleus cell bodies in Alzheimer's disease: mechanism of neuron death.
3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the neurotoxic monoamine oxidase A (MAO-A) metabolite of norepinephrine (NE). NE neurons in the locus ceruleus (LC) die in Alzheimer's disease (AD). To determine if DOPEGAL could contribute to NE neuron death in AD we measured levels of DOPEGAL, NE and their synthesizing enzymes in LC from AD and matched controls. We found 2.8- and 3.6-fold increases in DOPEGAL and MAO-A in AD LC neuronal cell bodies compared to controls. NE and dopamine beta-hydroxylase were increased by 3.8- and 10.7-fold, respectively. Implications for the mechanism of neuron death in AD are discussed.
Burke
W J
WJ
Department of Neurology, Saint Louis University Medical School, 3635 Vista at Grand, Saint Louis, MO 63110, USA.
Li
S W
SW
Schmitt
C A
CA
Xia
P
P
Chung
H D
HD
Gillespie
K N
KN
D000368:Aged; D000447:Aldehydes / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002396:Catechols; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*
D000447:Aldehydes; D002396:Catechols; D009498:Neurotoxins; C007431:3,4-dihydroxyphenylglycolaldehyde; D008995:Monoamine Oxidase; D009638:Norepinephrine