Monoaminergic neurotransmitters in Alzheimer's disease

Herregodts, Patrick; Bruyland, M.; Keyser, Jacques De; C, Solheid; Michotte, Yvette; Ebinger, Guy

doi:10.1016/0022-510x(89)90179-2

Cited by 35 publications

(9 citation statements)

References 42 publications

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“…[ 54 ], although no MHPG levels were measured and only five patients per group were included. Accordingly, MHPG and NA levels across the cortex of AD subjects have been reported to be significantly increased and decreased, respectively, compared to control values [ 55 ]. However, the only study that comes close in comparing brain MHPG levels between DLB and AD patients, is that from Langlais et al .…”

Section: Discussionmentioning

confidence: 99%

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer’s disease

et al. 2015

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IntroductionDepression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present.MethodsEleven behaviorally relevant brain regions of the left frozen hemisphere of 10 neuropathologically confirmed AD patients with/without depression (AD + D/-D; 5 were psychotic within AD + D), 10 confirmed DLB patients, all of whom were depressed (DLB + D; 5 psychotic patients), and, finally, 10 confirmed control subjects were regionally dissected. All patients were retrospectively assessed before death using the Behavioral Pathology in Alzheimer’s Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia amongst others. The concentrations of dopamine (DA), serotonin (5-HT), (nor)adrenaline and respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined using reversed-phase high-performance liquid chromatography with electrochemical detection.ResultsDLB subjects had the overall lowest monoamine and metabolite concentrations regarding 33 out of 41 significant monoaminergic group alterations. Moreover, MHPG levels were significantly decreased in almost 8 out of 11 brain regions of DLB- compared to AD patients. We also observed the lowest 5-HT and 5-HIAA levels, and 5-HIAA/5-HT turnover ratios in DLB + D compared to AD + D subjects. Additionally, a 4- and 7-fold increase of DOPAC/DA and HVA/DA turnover ratios, and, a 10-fold decrease of thalamic DA levels in DLB + D compared to AD + D patients and control subjects was noticed. Regarding psychosis, hippocampal DA levels in the overall DLB group significantly correlated with Behave-AD AB scores. In the total AD group, DA levels and HVA/DA ratios in the amygdala significantly correlated with Behave-AD AB scores instead.ConclusionsMonoaminergic neurotransmitter alterations contribute differently to the pathophysiology of depression and psychosis in DLB as opposed to AD, with a severely decreased serotonergic neurotransmission as the main monoaminergic etiology of depression in DLB. Similarly, psychosis in DLB might, in part, be etiologically explained by dopaminergic alterations in the hippocampus, whereas in AD, the amygdala might be involved.

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Section: Discussionmentioning

confidence: 99%

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer’s disease

et al. 2015

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“…This increased metabolism of norepinephrine is a possible cause of the decreased norepinephrine levels. On the other hand, a number of studies have shown no change in norepinephrine levels in different brain regions or cerebrospinal fluid (CSF) in both sporadic and familial AD cases (Sparks et al, 1988; Herregodts et al, 1989; Tohgi et al, 1992). In addition, increased norepinephrine levels were reported, which correlated with decreased cognitive function (Tohgi et al, 1992) and aging (Elrod et al, 1997) in AD patients.…”

Section: Noradrenergic Changes In Admentioning

confidence: 99%

Noradrenergic dysfunction in Alzheimer's disease

et al. 2015

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The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

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“…A heterogenous degeneration of multiple neuronal networks may reflect a generalized brain disorder relating to senile dementia of Alzheimer type (SDAT) (Quinn et al, 1986;Jellinger, 1991;Griffiths et al, 1994). Neurochemical and immunohistochemical studies suggest al least three dementia syndromes in PD: the most common is a consequence of dopamine deficiency, another results from combined dopaminergic and cholinergic deficiencies (Kawakatsu et al, 1990;Jellinger, 1986;Konings et al, 1995) and a third represents combined PD and SDAT with an additional varying involvement of other neurotransmitters, like serotonin (Gottfries et al, 1983;Herregodts et al, 1989) and SDAT-typical neuromodulators such as somatostatin (Leake and Ferrier, 1993;Unsicker, 1993;Hartikainen et al, 1992).…”

Section: Introductionmentioning

confidence: 98%

Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease ? effect of L-Dopa

Strittmatter

Hamann

Strubel³

et al. 1996

J. Neural Transmission

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There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).

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Monoaminergic neurotransmitters in Alzheimer's disease

Cited by 35 publications

References 42 publications

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer’s disease

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer’s disease

Noradrenergic dysfunction in Alzheimer's disease

Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease ? effect of L-Dopa

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