Navigating Neuropsychology 180 | Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE) – A Conversation With Dr. David Wolk
Dec 1, 2025
In this enlightening discussion, Dr. David Wolk, a neurology professor and director at the Penn Alzheimer's Disease Research Center, delves into Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE). He unpacks the role of TDP-43, its ties to ALS and hippocampal sclerosis, and contrasts LATE's clinical profile with Alzheimer's. Wolk highlights crucial diagnostic criteria, advanced neuroimaging markers, and the significance of understanding LATE's prevalence as we age. His insights pave the way for better identification and management of this complex condition.
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TDP-43's Dual Pathogenic Role
- TDP-43 aggregates reflect both loss of nuclear function and cytoplasmic accumulation that disturb RNA splicing.
- This dual gain/loss mechanism may underlie LATE's neurodegenerative effects.
LATE Is A Distinct Limbic Sequence
- LATE was defined to capture a limbic-predominant TDP-43 sequence distinct from FTLD and ALS.
- The pathology typically starts in the amygdala then spreads to hippocampus and anterior temporal regions.
LATE Is Common In The Oldest Old
- LATE prevalence rises steeply with age and likely affects ~30–40% of people over 80 in autopsy cohorts.
- Many older adults have mixed pathologies, so single-pathology prevalence estimates are uncertain.
