Journal Article DZNE-2023-00841

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

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2023
Wiley-Blackwell Oxford [u.a.]

Neuropathology & applied neurobiology 49(4), e12921 () [10.1111/nan.12921]

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Abstract: 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.The present retrospective study sought to provide novel details about the relationship between FTLD-TDP pathology and the presence of psychotic symptoms during life.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.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.

Keyword(s): Humans (MeSH) ; C9orf72 Protein: genetics (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Frontotemporal Dementia: pathology (MeSH) ; Frontotemporal Lobar Degeneration: pathology (MeSH) ; Psychotic Disorders: complications (MeSH) ; Retrospective Studies (MeSH) ; ALS ; FTLD-TDP ; frontotemporal dementia ; histology ; psychosis ; C9orf72 Protein ; DNA-Binding Proteins ; TARDBP protein, human

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Contributing Institute(s):
  1. Molecular Neuropathology of Neurodegenerative Diseases (AG Neumann)
Research Program(s):
  1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023
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Medline ; Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 ; OpenAccess ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection
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 Record created 2023-08-30, last modified 2024-04-03


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