Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Alzheimer Disease / drug therapy
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Benzamides / pharmacokinetics
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Benzamides / therapeutic use
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Binding Sites
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Choline O-Acetyltransferase / metabolism
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Cognition Disorders / etiology
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Cognition Disorders / metabolism*
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Female
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Frontal Lobe / drug effects
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Frontal Lobe / pathology
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Frontal Lobe / physiopathology
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Humans
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Isotopes / pharmacokinetics
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Male
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Memory Disorders / etiology
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Memory Disorders / metabolism
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Mental Status Schedule
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Neuropsychological Tests
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Piperazines / pharmacokinetics
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Pyridines / pharmacokinetics
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Pyridines / therapeutic use
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Receptor, Serotonin, 5-HT1B / physiology*
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Receptors, Serotonin / physiology*
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Serotonin Antagonists / pharmacokinetics
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Serotonin Antagonists / therapeutic use
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Serotonin Receptor Agonists / pharmacokinetics
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Statistics as Topic
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Sulfonamides / pharmacokinetics
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Temporal Lobe / drug effects
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Temporal Lobe / pathology
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Temporal Lobe / physiopathology
Substances
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Benzamides
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Isotopes
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N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl)-3-methyl-4-(4-pyridyl)benzamide
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Piperazines
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Pyridines
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Receptor, Serotonin, 5-HT1B
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Receptors, Serotonin
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SB 258585
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Sulfonamides
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serotonin 6 receptor
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Choline O-Acetyltransferase