TY  - JOUR
AU  - Görß, Doreen
AU  - Kilimann, Ingo
AU  - Dyrba, Martin
AU  - Nitsch, Sascha
AU  - Krause, Bernd
AU  - Teipel, Stefan
TI  - LATE: Nicht jede Demenz ist Alzheimer – Diskussion einer neuen Krankheitsentität am Fallbeispiel : Zum aktuellen Stand der „limbic-predominant age-related TDP-43 encephalopathy“ (LATE).
JO  - Der Nervenarzt
VL  - 92
IS  - 1
SN  - 1433-0407
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2021-00109
SP  - 18 - 26
PY  - 2021
AB  - Limbic-predominant age-related TDP-43 (Transactivation response(TAR)-DNA-binding protein 43 kDa) encephalopathy (LATE) has recently been characterized as a distinct neuropathological entity within the spectrum of dementia. Neuropathological alterations in the sense of LATE were already previously described as a comorbidity to Alzheimer's disease (AD) and it has been diagnosed independently from AD pathology in autopsy studies since 2008. The framework of LATE would account for the pathogenetic impact of limbic TDP-43 proteinopathy as a driver of amnestic dementia, either together with comorbid typical AD changes or as a distinct feature. The LATE possibly explains divergent clinical observations and biomarker results in patients suffering from severe amnestic impairment without biomarker evidence of AD-related amyloid and tau alterations. Whether LATE represents a distinct neuropathological entity or is part of the spectrum of neurodegenerative diseases associated with TDP-43 is currently a matter of debate. Further studies on the role of TDP-43 in the development of amnestic dementia are urgently needed. Thus, the enrichment of an amnestic phenotype in amyloid-centered therapeutic drug studies bears the risk of higher rates of patients with TDP-43 comorbidity, which could hinder the proof of efficacy in such trials. This article presents the current state of the discussion on LATE and illustrates the concept and the clinical considerations with a case study.
KW  - Alzheimer Disease: diagnosis
KW  - Alzheimer Disease: epidemiology
KW  - DNA-Binding Proteins: genetics
KW  - Humans
KW  - TDP-43 Proteinopathies: genetics
KW  - Alzheimer’s disease (Other)
KW  - Dementia (Other)
KW  - Proteinopathy (Other)
KW  - SNAP (Other)
KW  - TDP-43 (Other)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - TARDBP protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32409844
C2  - pmc:PMC7809002
DO  - DOI:10.1007/s00115-020-00922-z
UR  - https://pub.dzne.de/record/154248
ER  -