Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy

Authors

David A. Wolk
Peter T. Nelson
Liana Apostolova
Konstantinos Arfanakis
Patricia A. Boyle
Cynthia M. Carlsson
Nick Corriveau-Lecavalier
Penny Dacks
Bradford C. Dickerson
Gladys E. Maestre, The University of Texas Rio Grande Valley School of MedicineFollow

Document Type

Article

Publication Date

1-2025

Abstract

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC). HIGHLIGHTS: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a highly prevalent driver of neuropathologic memory loss in late life. LATE neuropathologic change (LATE-NC) is a common co-pathology with Alzheimer's disease neuropathologic change (ADNC) and may influence outcomes with emerging disease-modifying medicines. We provide initial clinical criteria for diagnosing LATE during life either when LATE-NC is the likely primary driver of symptoms or when observed in conjunction with AD. Definitions of possible and probable LATE are provided.

Comments

© 2025 The Author(s). Alzheimer's & Dementiapublished by Wiley Periodicals LLC on behalf of Alzheimer's Association.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Recommended Citation

Wolk, D. A., Nelson, P. T., Apostolova, L., Arfanakis, K., Boyle, P. A., Carlsson, C. M., ... & Schneider, J. A. (2025). Clinical criteria for Limbic‐Predominant age‐related TDP‐43 encephalopathy. Alzheimer's & Dementia, 21(1), e14202. https://doi.org/10.1002/alz.14202

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Alzheimer's & Dementia

DOI

10.1002/alz.14202

Academic Level

faculty

Mentor/PI Department

Neuroscience