title: Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease.
abstract: OBJECTIVE
  People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert.
  
  
  METHODS
  High-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested.
  
  
  RESULTS
  PD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups.
  
  
  CONCLUSIONS
  These results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia.
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri ; Department of Developmental Biology, Washington University School of Medicine St. Louis, Missouri ; Hope Center for Neurological Disorders, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Chandana
authors.initials: C
authors.lastname: Buddhala
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Loftin
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Kuley
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri ; Hope Center for Neurological Disorders, Washington University School of Medicine St. Louis, Missouri ; Department of Pathology and Immunology, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri ; Department of Radiology, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Campbell
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri ; Hope Center for Neurological Disorders, Washington University School of Medicine St. Louis, Missouri ; Department of Radiology, Washington University School of Medicine St. Louis, Missouri ; Department of Anatomy and Neurobiology, Washington University School of Medicine St. Louis, Missouri ; Program in Occupational Therapy, Washington University School of Medicine St. Louis, Missouri ; Program in Physical Therapy, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, Missouri ; Department of Developmental Biology, Washington University School of Medicine St. Louis, Missouri ; Hope Center for Neurological Disorders, Washington University School of Medicine St. Louis, Missouri.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kotzbauer