AccScience Publishing / AN / Online First / DOI: 10.36922/an.2603
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REVIEW

Limbic-predominant age-related TDP-43 encephalopathy: Amnestic-predominant cognitive decline beyond Alzheimer’s disease

Miren Maltuna1,2,3*
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1 Center for Research and Advanced Therapies, CITA-Alzhéimer Foundation, Donostia-San Sebastian, Spain
2 Debabarrena Integrated Health Organization, Osakidetza Basque Health Service, Gipuzkoa, Spain
3 Department of Medicine, Faculty of Health Sciences, University of Deusto, Bilbo, Bizkaia, Spain
Advanced Neurology, 2603 https://doi.org/10.36922/an.2603
Submitted: 1 January 2024 | Accepted: 15 March 2024 | Published: 23 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Alzheimer’s disease (AD) is the main cause of neurodegenerative cognitive impairment leading to dementia. It is characterized by progressively worsening cognitive impairment with a predominant amnestic involvement. However, it is not the sole neurodegenerative disease presenting such symptoms, particularly prevalent among the elderly in our society. Recently, limbic-predominant age-related TDP-43 encephalopathy (LATE) has been identified. The diagnosis of LATE in living individuals is very complex due to the lack of universally applicable diagnostic criteria and reliable biomarkers. Nonetheless, its relevance is not diminished, as up to 20% of cases diagnosed with AD, especially in individuals over 80 years old, are actually due to LATE, and over 50% of AD cases have associated LATE copathology. This narrative review aims to address several aspects related to LATE, including identifying its typical clinical features, gaining a better understanding of its pathogenesis in pure cases and those associated with other neurodegenerative diseases, advancements in diagnostic tools for detecting LATE during life, its anatomopathological definition and staging, and potential advances in treatment. In the current era of potentially disease-modifying anti-amyloid treatments for AD, understanding both pure LATE and its co-pathology with AD is of particular relevance.

Keywords
Cognitive impairment
TDP-43
Alzheimer’s disease
Biomarkers
Funding
None.
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The author declares that she has no competing interests.
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