Presynaptic Serotonergic Markers in Community‐Acquired Cases of Alzheimer's Disease: Correlations with Depression and Neuroleptic Medication

Chen, C. P. L.-H.; Alder, Janet; Bowen, David M.; Esiri, Margaret M.; McDonald, B.; Hope, Tony; Jobst, K; Francis, Paul T.

doi:10.1046/j.1471-4159.1996.66041592.x

Cited by 126 publications

(81 citation statements)

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“…Despite the fact that alterations in markers of serotonergic innervation have been linked to clinical indices of cognition and behavioral abnormalities in AD (Chen et al, 1995;Chen et al, 1996;Forstl et al, 1994;Linnoila and Virkkunen, 1992;Zubenko et al, 1991), the role of the different serotonergic receptors in the illness remains unclear. Alterations in the expression of serotonergic receptors such as 5-HT 1A , 5-HT 2 , or 5-HT 4 receptors have already been described in AD (Cheng et al, 1991;Cross, 1990;Lai et al, 2002;Palmer et al, 1987b), whereas the density of 5-HT 3 receptors does not seem to be affected by the illness (Barnes et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, even though there is no specific center in the brain for a distinctive BPSD, the organization of the ascending serotonergic neuron projections and the widespread distribution of serotonergic terminals in cortical and limbic areas indicate that these projections are the most likely to be involved in the regulation of behavioral and mood disorders (Barnes and Sharp, 1999). In this sense, the serotonergic system has been widely implicated in depression (Chen et al, 1996;Meltzer et al, 1998), psychosis (Garcia-Alloza et al, submitted; Jones and Blackburn, 2002), and aggression (Berman, 1997;Procter et al, 1992). …”

Section: Introductionmentioning

confidence: 99%

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Differential Involvement of 5-HT1B/1D and 5-HT6 Receptors in Cognitive and Non-cognitive Symptoms in Alzheimer's Disease

García-Alloza

Hirst

Chen

et al. 2003

Neuropsychopharmacol

137

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Growing evidence suggests that a compromised serotonergic system plays an important role in the pathophysiology of Alzheimer's disease (AD). We assessed the expression of 5-HT 1B/1D and 5-HT 6 receptors and cholinacetyltransferase (ChAT) activity in post-mortem frontal and temporal cortex from AD patients who had been prospectively assessed for cognitive function using the Mini-Mental State Examination (MMSE) and behavioral changes using the Present Behavioral Examination (PBE). 5-HT 1B/1D and 5-HT 6 receptor densities were significantly reduced in both cortical areas. 5-HT 1B/1D receptor density was correlated to MMSE decline in the frontal cortex, supporting its implication in memory impairment. The best predictor for lowered 5-HT 6 receptor density in the temporal cortex was the PBE measure of overactivity. The 5-HT 6 /ChAT ratio was related to aggression both in the frontal and temporal cortex. Therefore, antagonists acting at 5-HT 6 receptors could be useful in the treatment of non-cognitive symptoms associated to AD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Involvement of 5-HT1B/1D and 5-HT6 Receptors in Cognitive and Non-cognitive Symptoms in Alzheimer's Disease

García-Alloza

Hirst

Chen

et al. 2003

Neuropsychopharmacol

137

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“…In AD, previous reports have shown extensive serotonergic denervation (Chen, Alder, & Bowen, 1996;Chen et al, 2000) although its clinical signification has been only partially defined. Serotonin (5-HT) has also been involved in many psychobiological functions such as aggression, depression, anxiety, or psychosis that are relevant to BPSD (Chen et al, 1996;Lancot et al, 2001). In this context, open label trials with selective serotonin reuptake inhibitors (SSRIs) have been associated with improvements in BPSD in a high proportion of patients (Parnetti, Amici, Lanari, & Gallai, 2001).…”

Section: Introductionmentioning

confidence: 98%

“…Consequently, it has been argued that serotonin plays a role in the maintenance of behavioral capacities in the face of reduced cholinergic transmission (Dringenberg & Zalan, 1999). In AD, previous reports have shown extensive serotonergic denervation (Chen, Alder, & Bowen, 1996;Chen et al, 2000) although its clinical signification has been only partially defined. Serotonin (5-HT) has also been involved in many psychobiological functions such as aggression, depression, anxiety, or psychosis that are relevant to BPSD (Chen et al, 1996;Lancot et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease

et al. 2005

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Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.

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“…Deficiencies in central serotonergic [12][13][14][15] and perhaps dopaminergic [16], but see also [17,18] neural transmission may also play a critical role in some of the clinical manifestations of AD. Significant reductions in γ-amino butyric acid (GABA) levels have also been described in cases of AD [19].…”

Section: Introductionmentioning

confidence: 99%

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

Aisa

Gil-Bea

Solas

et al. 2010

JAD

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Abstract. Neurotransmitter system dysfunction and synapse loss have been recognized as hallmarks of Alzheimer's disease (AD). Our hypothesis is that specific neurochemical populations of neurons might be more vulnerable to degeneration in AD due to particular deficits in synaptic plasticity. We have studied, in postmortem brain tissue, the relationship between levels of synaptic markers (NCAM and BDNF), neurochemical measurements (cholinacetyltransferase activity, serotonin, dopamine, GABA, and glutamate levels), and clinical data (cognitive status measured as MMSE score). NCAM levels in frontal and temporal cortex from AD patients were significantly lower than control patients. Interestingly, these reductions in NCAM levels were associated to an ApoE4 genotype. Levels of BDNF were also significantly reduced in both frontal and temporal regions in AD patients. The ratio between plasticity markers and neurochemical measurements was used to study which of the neurochemical populations was particularly associated to plasticity changes. In both the frontal and temporal cortex, there was a significant reduction in the ChAT/NCAM ratio in AD samples compared to controls. None of the ratios to BDNF were different between control and AD samples. Furthermore, Pearson's product moment showed a significant positive correlation between MMSE score and the ChAT/NCAM ratio in frontal cortex (n = 19; r = 0.526*; p = 0.037) as well as in temporal cortex (n = 19; r = 0.601*; p = 0.018) in AD patients. Altogether, these data suggest a potential involvement of NCAM expressing neurons in the cognitive deficits in AD.

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Presynaptic Serotonergic Markers in Community‐Acquired Cases of Alzheimer's Disease: Correlations with Depression and Neuroleptic Medication

Cited by 126 publications

References 10 publications

Differential Involvement of 5-HT1B/1D and 5-HT6 Receptors in Cognitive and Non-cognitive Symptoms in Alzheimer's Disease

Differential Involvement of 5-HT1B/1D and 5-HT6 Receptors in Cognitive and Non-cognitive Symptoms in Alzheimer's Disease

Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease

Altered NCAM Expression Associated with the Cholinergic System in Alzheimer's Disease

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