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Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease

Takahiro Takeda1, Danielle Seilhean1, Isabelle Le Ber1

  • 1Service de Neuropathologie, Laboratoire Raymond Escourolle, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U1127, CNRS UMR 7225, Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, UPMC-P6 UMR S 1127, Hôpital de la Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Paris, France; Centre de Référence des Démences Rares, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Paris, France; Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan; and Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Journal of Neuropathology and Experimental Neurology
|September 2, 2017
PubMed

Insights

TDP-43 inclusions in the amygdala are common in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). Their density varies by subtype, with ventral basolateral nucleus involvement noted across all forms.

Area of Science:

  • Neuroscience
  • Neuropathology

Background:

  • TDP-43-positive inclusions characterize frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND), including amyotrophic lateral sclerosis.
  • Amygdala pathology is implicated in the behavioral abnormalities observed in FTLD.

Purpose of the Study:

  • To investigate the presence and distribution of TDP-43 inclusions in the amygdala across different subtypes of FTLD/MND.
  • To compare the numerical density and regional distribution of TDP-43 inclusions in sporadic FTLD/MND, C9ORF72-mutated FTLD/MND, and progranulin-mutated FTLD.

Main Methods:

  • Examination of TDP-43 inclusions in amygdala tissue from patients with sporadic FTLD/MND, FTLD/MND-C9, and FTLD-GRN.
  • Utilized conventional and immunological staining techniques.
  • Quantified the numerical density of TDP-43 inclusions on a regional basis within the amygdala.

Main Results:

  • TDP-43 inclusions were detected in sFTLD/MND (10/26), FTLD/MND-C9 (5/9), and FTLD-GRN (4/4) cases.
  • Numerical density of inclusions was lower in FTLD/MND-C9 compared to sFTLD/MND and FTLD-GRN.
  • TDP-43 inclusions were more numerous in the ventral region of the basolateral nucleus group across all subtypes, with this pattern being less evident in FTLD-GRN.

Conclusions:

  • TDP-43 inclusions are a common neuropathological feature in the amygdala across various FTLD/MND subtypes.
  • Differences in the subregional distribution of TDP-43 inclusions within the amygdala may correlate with distinct neuronal connectivity patterns affected in these diseases.
Keywords:
AmygdalaAmyotrophic lateral sclerosisC9ORF72Frontotemporal lobar degenerationMotor neuron diseaseProgranulinTDP-43

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