Psychotic symptoms in frontotemporal dementia with TDP-43 tend to be associated with type B pathology.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 7609829 Publication Model: Print Cited Medium: Internet ISSN: 1365-2990 (Electronic) Linking ISSN: 03051846 NLM ISO Abbreviation: Neuropathol Appl Neurobiol Subsets: MEDLINE

Original Publication: Oxford, Blackwell Scientific Publications.

Frontotemporal Dementia*/genetics ; Frontotemporal Dementia*/pathology ; Frontotemporal Lobar Degeneration*/pathology ; Psychotic Disorders*/complications; Humans ; C9orf72 Protein/genetics ; DNA-Binding Proteins/genetics ; Retrospective Studies

Aims: Psychotic symptoms are increasingly recognized as a distinguishing clinical feature in patients with dementia due to frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Within this group, carriers of the C9orf72 repeat expansion are particularly prone to develop delusions and hallucinations.
Methods: The present retrospective study sought to provide novel details about the relationship between FTLD-TDP pathology and the presence of psychotic symptoms during life.
Results: We found that FTLD-TDP subtype B was more frequent in patients with psychotic symptoms than in those without. This relationship was present even when corrected for the presence of C9orf72 mutation, suggesting that pathophysiological processes leading to the development of subtype B pathology may increase the risk of psychotic symptoms. Within the group of FTLD-TDP cases with subtype B pathology, psychotic symptoms tended to be associated with a greater burden of TDP-43 pathology in the white matter and a lower burden in lower motor neurons. When present, pathological involvement of motor neurons was more likely to be asymptomatic in patients with psychosis.
Conclusions: This work suggests that psychotic symptoms in patients with FTLD-TDP tend to be associated with subtype B pathology. This relationship is not completely explained by the effects of the C9orf72 mutation and raises the possibility of a direct link between psychotic symptoms and this particular pattern of TDP-43 pathology.
(© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

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P01 AG019724 United States AG NIA NIH HHS; U19 AG063911 United States AG NIA NIH HHS

Keywords: ALS; FTLD-TDP; frontotemporal dementia; histology; psychosis

0 (C9orf72 Protein)
0 (DNA-Binding Proteins)
0 (TARDBP protein, human)

Date Created: 20230630 Date Completed: 20230831 Latest Revision: 20240802

20240802

PMC10527970

10.1111/nan.12921

37386798