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Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and Biomarkers

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Abstract

Purpose of Review

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined neurodegenerative disease characterized by amnestic phenotype and pathological inclusions of TAR DNA-binding protein 43 (TDP-43). LATE is distinct from rarer forms of TDP-43 diseases such as frontotemporal lobar degeneration with TDP-43 but is also a common copathology with Alzheimer’s disease (AD) and cerebrovascular disease and accelerates cognitive decline. LATE contributes to clinicopathologic heterogeneity in neurodegenerative diseases, so it is imperative to distinguish LATE from other etiologies.

Recent Findings

Novel biomarkers for LATE are being developed with magnetic resonance imaging (MRI) and positron emission tomography (PET). When cooccurring with AD, LATE exhibits identifiable patterns of limbic-predominant atrophy on MRI and hypometabolism on 18F-fluorodeoxyglucose PET that are greater than expected relative to levels of local AD pathology. Efforts are being made to develop TDP-43-specific radiotracers, molecularly specific biofluid measures, and genomic predictors of TDP-43. LATE is a highly prevalent neurodegenerative disease distinct from previously characterized cognitive disorders.

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Acknowledgements

The authors thank our lab members for helpful discussions and for study investigators, staff, participants, and families for their support.

Funding

Funding was provided by the Ruth L. Kirschstein National Research Service Award (NIA F30 AG074524, Michael Tran Duong) and the University of Pennsylvania Alzheimer’s Disease Core Center grant (NIA P30 AG072979, David A. Wolk).

Author information

Authors and Affiliations

  1. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael Tran Duong & David A. Wolk

  2. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael Tran Duong

  3. Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA

    Michael Tran Duong

  4. Alzheimer’s Disease Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    David A. Wolk

  5. Institute On Aging, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA

    David A. Wolk

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  1. Michael Tran Duong
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  2. David A. Wolk
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Correspondence to David A. Wolk.

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David A. Wolk reports grants from Merck, Biogen, Eli Lilly/Avid and additional fees from GE Healthcare, Functional Neuromodulation and Neuronix, all outside of this work. Michael Tran Duong has no conflicts of interest to report.

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Duong, M.T., Wolk, D.A. Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and Biomarkers. Curr Neurol Neurosci Rep 22, 689–698 (2022). https://doi.org/10.1007/s11910-022-01232-4

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