TY - JOUR
T1 - Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry
AU - Ducharme, Simon
AU - Pijnenburg, Yolande
AU - Rohrer, Jonathan D.
AU - Huey, Edward
AU - Finger, Elizabeth
AU - Tatton, Nadine
N1 - Funding Information: Medical writing support was funded by Alector, Inc. Academic authors did not receive compensation from Alector for this work. SD has received: research funding support from Alnylam Pharmaceuticals, Biogen, Janssen, Novo Nordisk, and Wave Life Sciences; consultation fees from AI Therapeutics, Eisai, Prevail Therapeutics/Eli Lilly, and QuRALIS; and support for meeting attendance/travel from Eisai. SD has participated in advisory boards/DSMBs for IntelGenX. YP has nothing to disclose. JDR has received consulting fees paid to his institution from AC Immune SA, Astex Pharmaceuticals, Biogen, Eisai, Takeda, and UCB. JDR has participated in advisory boards/DSMBs for Alector, Arkuda Therapeutics, Prevail Therapeutics, and Wave Life Sciences. EH has received support from NIH grants R01MH120794 and R01AG062268. EF has received research support from Canadian Institutes of Health Research, the Physicians' Services Incorporated Foundation, and the Weston Foundation and has participated in scientific advisory boards and received honoraria from Denali Therapeutics and Vigil Neuro, and has received honoraria for serving as an Annual Meeting Course Director with the American Academy of Neurology. NT is an employee of Alector, LLC, may have an equity interest in Alector, Inc, and is an unpaid board member for CurePSP. Publisher Copyright: © 2023 The Authors
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - Frontotemporal dementia
KW - amyotrophic lateral sclerosis
KW - differential diagnosis
KW - limbic predominant age related TDP-43 encephalopathy (LATE)
KW - neuropsychiatric symptoms
UR - http://www.scopus.com/inward/record.url?scp=85172458480&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jagp.2023.08.017
DO - https://doi.org/10.1016/j.jagp.2023.08.017
M3 - Review article
C2 - 37741764
SN - 1064-7481
VL - 32
SP - 98
EP - 113
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 1
ER -