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Advanced Neurology

REVIEW ARTICLE
Limbic-predominant age-related TDP-43

encephalopathy: Amnestic-predominant
cognitive decline beyond Alzheimer’s disease

Miren Altuna 1,2,3 *

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

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
*Corresponding author:
Miren Altuna typical clinical features, gaining a better understanding of its pathogenesis in pure
(maltuna@cita-alzheimer.org) cases and those associated with other neurodegenerative diseases, advancements
in diagnostic tools for detecting LATE during life, its anatomopathological definition
Citation: Altuna, M. Limbic-
predominant age-related and staging, and potential advances in treatment. In the current era of potentially
TDP-43 encephalopathy: Amnestic- disease-modifying anti-amyloid treatments for AD, understanding both pure LATE
predominant cognitive decline and its co-pathology with AD is of particular relevance.
beyond Alzheimer’s disease. Adv
Neuro. 2024;3(2):2603.
doi: 10.36922/an.2603
Keywords: Cognitive impairment; TDP-43; Alzheimer’s disease; Biomarkers
Received: January 1, 2024
Accepted: March 15, 2024
Published Online: May 23, 2024 1. Introduction
Copyright: © 2024 Author(s).
This is an Open-Access article The comprehensive approach to cognitive impairment poses a new challenge for
distributed under the terms of the developed societies experiencing an exponential increase in life expectancy. Population
Creative Commons Attribution aging is related to the increase in the prevalence of various causes of cognitive impairment,
License, permitting distribution,
and reproduction in any medium, both neurodegenerative and non-neurodegenerative. While Alzheimer’s disease (AD)
1,2
provided the original work is remains the most prevalent neurodegenerative cause, it is not the sole contributor. At
properly cited. present, it is advocated that diagnosis should occur in the early clinical stages, such as
Publisher’s Note: AccScience mild cognitive impairment, before individuals lose functional autonomy or progress to
Publishing remains neutral with dementia. Ideally, this diagnosis should not solely rely on clinical evaluation but should
regard to jurisdictional claims in
published maps and institutional also be supported by biomarker diagnosis, making the diagnostic process a combination
affiliations. of clinical and biological assessments.

Volume 3 Issue 2 (2024) 1 doi: 10.36922/an.2603