Biochemical Assessment of Serotonergic and Cholinergic Dysfunction and Cerebral Atrophy in Alzheimer's Disease

Abstract

Markers of serotonin synapses in entire temporal lobe and frontal and temporal neocortex were examined for changes in Alzheimer's disease by use of both neurosurgical and autopsy samples. Uptake of [3H]serotonin, binding of [3H]imipramine, and content of indolamines were all significantly reduced, indicating that serotonin nerve terminals are affected. Binding of [3H]serotonin was also reduced, whereas that of [3H]quinuclidinyl benzilate, [3H]muscimol, and [3H]dihydroalprenolol were unaltered. When the Alzheimer's samples were subdivided according to age, the reduction in [3H]serotonin binding was a feature of only autopsy samples from younger patients. In contrast, presynaptic cholinergic activity was reduced in all groups of Alzheimer's samples, including neurosurgical specimens. Five markers, thought to reflect cerebral atrophy, cytoplasm, nerve cell membrane, and neuronal perikarya were measured in the entire temporal lobe. In Alzheimer's disease the reductions (mean 25%, range 20-35%) were thought to be too large to be due only to loss of structures associated with the presumed cholinergic perikarya in the basal forebrain and monoamine neurones in the brain stem.

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

“…There is considerable regional variation in the increase of ACh levels after HupA administration, with maximal increase seen in frontal and parietal cortex, and smaller increases in the striatum and cerebellum [31] . Considering that ACh level is particularly low in the cerebral cortex of patients with AD [57] , this particular regional specificity produced by HupA may constitute a therapeutic advantage. A positive correlation was seen between ACh levels and AChE activity in the frontal cortex and whole brain [13,31,32,53] .…”

Alzheimer’s disease: amino acid levels and brain metabolic status

“…Studies conducted on antemortem cerebral biopsy in neocortex of patients with AD show not only that neurotransmitter systems (cholinergic, noradrenergic, serotonergic and glutamergic neurons) and pyramidal neurons are prematurely damaged in the course of the disease [2], but also that the loss of cholinergic and pyramidal neurons is related to the severity of dementia evolution [3]. The molecular etiology of AD is still incomplete.…”

Dynamic Neurotransmitter Interactions Measured with PET

“…These cholinergic intemeurons provide excitatory input to local GABA neurons, which in turn are thought to inhibit the activity of dopaminergic neurons (Bunney and Aghaj anian, 1976). et al, 1990a (Wesemann et al, 1983;Stanley and Mann, 1984;Pucilowski and Kostowski, 1983;Bowen et al, 1983;Crow et al, 1984;Middlemiss et al, 1986;Reynolds et al, 1984 (Joyce et al, 1993;Joyce, 1993;Zazpe et al, 1994); (Kapur and Remington, 1996 (Tsukada et al, 1999).…”