Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapy.
Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Crain
B J
BJ
Bell
J M
JM
Bissette
G
G
Nemeroff
C B
CB
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D006801:Humans; D009928:Organ Specificity; D013569:Synapses / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*
D002795:Choline O-Acetyltransferase; D002794:Choline