Serotonin-1A receptor binding to frontal cortex in dementia with lewy bodies and parkinson’s disease dementia

Sally I Sharp1, Clive G Ballard1, Iryna Ziabrev 2,3, Elaine K Perry2, Dag Aarsland3,4, Jan-Petter Larsen3,4 & Paul T Francis1. 1Wolfson Centre for Age-Related Diseases, Guy’s Campus, King’s College London, SE1 1UL. 2Institute for Ageing and Health, University of Newcastle, UK. 3Centre for Neuropsychiatric and Gerontopsychiatric Research, Central Hospital of Rogaland, Stavanger, Norway. 4School of Medicine, University of Bergen.

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are common late onset dementias associated with α-synuclein pathology . The neurochemical profile of DLB and PDD is less established than that of Alzheimer’s disease (AD) and there is some debate as to whether these severe dementias are part of a spectrum or are distinct clinical entities (McKeith, 2000; Aarsland, 2004).

Serotonin 1A receptors (5-HT1A) cause neuronal inhibition and are implicated in mood, aggressive behaviours and cognition in AD (Lai et al., 2002; 2003). Thus it is of value to investigate serotonergic parameters and their relationship to important neuropsychiatric symptoms in parkinsonian dementias. The aim of this study was to determine 5-HT1A status in frontal cortex of brains from people with dementia.

Membranes were prepared by three centrifugation and resuspension cycles from f rontal cortex (Brodmann Area 9) from 13 DLB cases, 14 PDD and 10 controls (mean a ge at death ± s.e.mean: 79.0 ± 4.0, 80.4 ± 1.9, and 77.2 ± 3.2 years respectively) . Homogenates were examined for density (Bmax) and affinity (KD) of 3H 8-Hydroxy-2-dipropylaminotetralin (8-OH-DPAT ) binding to 5-HT1A (as described, Lai et al., 2002).

Table 1. Specific binding of 3H 8-OH-DPAT to 5-HT1A in frontal cortex.

Values are mean ± s.e.mean (n). * Significantly different from PDD at P = 0.008, one-way ANOVA Bonferroni post hoc test.

Patients with DLB had a significantly higher Bmax value for 8-OH-DPAT compared with PDD, however, neither value was significantly different from control ( Table 1) . There was no significant alteration in KD for 8-OH-DPAT binding in dementia patients and control . Relative preservation of 5-HT1A in DLB and loss in PDD suggests a distinct neurochemical feature of the two dementias and could relate to symptomatic traits, such as hallucinations, with implications for treatment. Further analyses are required to determine possible associations between 5-HT1A binding in the frontal cortex with cognitive decline and behavioural disorders in dementia. Furthermore, it is necessary to investigate the status of 5-HT1A in the temporal cortex of these DLB and PDD patients.

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This work was supported by local funds.