title: Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease.
abstract: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during the disease course of nearly all AD patients and consist of psychosis, agitation/aggression, and depression, among others. Given their detrimental consequences regarding life expectancy, cognition, and socio-economic costs, it is essential to elucidate their neurochemical etiology to facilitate the development of novel and effective pharmacotherapeutics. This study attempted to identify brain region-specific monoaminergic correlates of NPS by measuring the levels of eight monoamines and metabolites in nine relevant postmortem brain regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA), serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3-indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP-HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of monoaminergic neurotransmitter alterations were calculated. As a result, MMSE scores, used as a measure of dementia severity, correlated positively with hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely correlated with agitation scores, whereas thalamic MHPG levels comparably did with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA ratios, indicative of DA turnover, correlated with physically agitated behavior while MHPG levels correlated with affective disturbances. These findings support the assumption that specific NPS features in AD might be (in)directly related to brain region-specific monoaminergic neurotransmitter alterations. Additionally, the effect of AD pathology on neurochemical alterations in the cerebellum requires further examination due to its important but underestimated role in the neurochemical pathophysiology of NPS in AD.
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vermeiren
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Aerts
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium University of Groningen, University Medical Center Groningen (UMCG), Department of Neurology and Alzheimer Research Center, Groningen, The Netherlands Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D001344:Autopsy; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D055664:Electrochemical Techniques; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011618:Psychotic Disorders / Q000209:etiology*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid
keywords: Alzheimer's disease; behavior; brain tissue; correlations; dementia; monoamines and metabolites; neurochemistry; neuropsychiatric symptoms