Locus Coeruleus Degeneration Differs Between Frontotemporal Lobar Degeneration Subtypes

J Alzheimers Dis. 2022;89(2):463-471. doi: 10.3233/JAD-220276.

Abstract

Background: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy.

Objective: The aim of this study was to investigate the LC in FTLD subgroups.

Methods: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro- and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a group with vascular cognitive impairment (VCI) served as comparison groups.

Results: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (N = 151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro- and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group.

Conclusion: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging.

Keywords: Frontotemporal dementia; TDP-43; locus coeruleus; neuronal counts; tau; tauopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Frontotemporal Dementia* / psychology
  • Frontotemporal Lobar Degeneration* / diagnosis
  • Humans
  • Locus Coeruleus / pathology

Substances

  • DNA-Binding Proteins
  • TARDBP protein, human