Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry

Simon Ducharme, Yolande Pijnenburg, Jonathan D. Rohrer, Edward Huey, Elizabeth Finger, Nadine Tatton

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)

Abstract

Neuropsychiatric symptoms (NPS) are common manifestations of neurodegenerative disorders and are often early signs of those diseases. Among those neurodegenerative diseases, TDP-43 proteinopathies are an increasingly recognized cause of early neuropsychiatric manifestations. TDP-43–related diseases include frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE). The majority of TDP-43–related diseases are sporadic, but a significant proportion is hereditary, with progranulin (GRN) mutations and C9orf72 repeat expansions as the most common genetic etiologies. Studies reveal that NPS can be the initial manifestation of those diseases or can complicate disease course, but there is a lack of awareness among clinicians about TDP-43–related diseases, which leads to common diagnostic mistakes or delays. There is also emerging evidence that TDP-43 accumulations could play a role in late-onset primary psychiatric disorders. In the absence of robust biomarkers for TDP-43, the diagnosis remains primarily based on clinical assessment and neuroimaging. Given the association with psychiatric symptoms, clinical psychiatrists have a key role in the early identification of patients with TDP-43–related diseases. This narrative review provides a comprehensive overview of the pathobiology of TDP-43, resulting clinical presentations, and associated neuropsychiatric manifestations to help guide clinical practice.
Original languageEnglish
Pages (from-to)98-113
Number of pages16
JournalAmerican Journal of Geriatric Psychiatry
Volume32
Issue number1
Early online date2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • Frontotemporal dementia
  • amyotrophic lateral sclerosis
  • differential diagnosis
  • limbic predominant age related TDP-43 encephalopathy (LATE)
  • neuropsychiatric symptoms

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