Presynaptic dopaminergic function in early-onset Alzheimer's disease: an FP-CIT image study

Neurobiol Aging. 2020 Feb:86:75-80. doi: 10.1016/j.neurobiolaging.2019.10.007. Epub 2019 Oct 21.

Abstract

We aimed to investigate whether amyloid-β (Aβ) positive early-onset Alzheimer's disease (EOAD) patients have presynaptic dopaminergic deficits on in vivo 18F-FP-CIT PET imaging. We enrolled 34 EOAD patients and 9 cognitively normal controls (NC), all of whom underwent 18F-florbetaben and 18F-FP-CIT PET at Samsung Medical Center. We assessed motor symptoms using Unified Parkinson's Disease Rating Scale (UPDRS) and divided the EOAD patients into 2 groups using a UPDRS cutoff of 10. We compared regional florbetaben and FP-CIT uptake across the NC and the 2 EOAD groups with lower and higher UPDRS and investigated the associations between regional florbetaben or FP-CIT uptake and UPDRS in EOAD patients. Among the 30 EOAD patients who were Aβ positive on florbetaben PET, the higher UPDRS (>10) group (n = 9) had a longer disease duration (7.2 ± 3.3 vs. 4.1 ± 1.8, p = 0.002), and had a tendency to have lower Mini-Mental State Examination (9.6 ± 7.9 vs. 15.0 ± 6.0, p = 0.052) than the lower UPDRS (≤10) group (n = 21). Across the NC and the 2 EOAD groups, there were no significant differences in FP-CIT uptake in caudate (p = 0.122) and putamen (p = 0.685) or florbetaben uptake in midbrain (p = 0.890). Finally, regression analyses showed that UPDRS was not associated with FP-CIT uptake in caudate (p = 0.913) or putamen (p = 0.407), or with florbetaben PET uptake in caudate (p = 0.553), putamen (p = 0.617), midbrain (p = 0.843), or global cortex (p = 0.658). This study showed that parkinsonian signs in EOAD patients may be related with mechanisms other than presynaptic dopaminergic deficit. Our finding is clinically important because it suggests that L-dopa treatment in EOAD with parkinsonian signs may not improve motor symptoms.

Keywords: Alzheimer's disease; Amyloid PET; FP-CIT PET; PET; Parkinson's disease/parkinsonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Dopamine / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Presynaptic Terminals / physiology*
  • Retrospective Studies

Substances

  • Amyloid beta-Peptides
  • Dopamine