Faculty, Staff and Student Publications
Publication Date
1-1-2025
Journal
Alzheimer's & Dementia
DOI
10.1002/alz.14202
PMID
39807681
PMCID
PMC11772733
PubMedCentral® Posted Date
1-14-2025
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Alzheimer Disease, Hippocampus, Limbic System, TDP-43 Proteinopathies, Dementia, Alzheimer's disease, dementia, limbic predominant age‐related TDP‐43 encephalopathy, mild cognitive impairment, multi‐etiology dementia
Published Open-Access
yes
Recommended Citation
Wolk, David A; Nelson, Peter T; Apostolova, Liana; et al., "Clinical Criteria for Limbic-Predominant Age-Related Tdp-43 Encephalopathy" (2025). Faculty, Staff and Student Publications. 6095.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6095
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