Striatal DAT and Extrastriatal SERT Binding in Early-Stage Parkinson's Disease and Dementia With Lewy Bodies, Compared With Healthy Controls: An 123 I-FP-CIT SPECT Study

Neuroimage Clin. 2019;22:101755. doi: 10.1016/j.nicl.2019.101755. Epub 2019 Mar 12.

Abstract

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD-left: F(1,29) = 28.778, P < .001, ω2 = 0.35; right: F(1,29) = 35.338, P < .001, ω2 = 0.42; DLB-left: F(1,29) = 28.241, P < .001, ω2 = 0.31; right: F(1,29) = 18.811, P < .001, ω2 = 0.26) and bilateral posterior putamen (PD-left: F(1,29) = 107.531, P < .001, ω2 = 0.77; right: F(1,29) = 87.525, P < .001, ω2 = 0.72; DLB-left: F(1,29) = 39.910, P < .001, ω2 = 0.48; right: F(1,29) = 26.882, P < .001, ω2 = 0.38). DLB patients had lower hypothalamic 123I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P = .020, ω2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.

Keywords: (123)I-FP-CIT; DAT; Dementia with Lewy bodies; Parkinson's disease; SERT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism*
  • Humans
  • Hypothalamus / diagnostic imaging
  • Hypothalamus / metabolism*
  • Lewy Body Disease / diagnostic imaging
  • Lewy Body Disease / metabolism*
  • Male
  • Middle Aged
  • Neostriatum / diagnostic imaging
  • Neostriatum / metabolism*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism*
  • Retrospective Studies
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Thalamus / diagnostic imaging
  • Thalamus / metabolism*
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Tropanes*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane