Limbic-predominant Age-related TDP-43 Encephalopathy (LATE): Clinical and Imaging Clues for an Underrecognized Dementia Entity
Valentina Velasco1, Andres Ricaurte-Fajardo2
1School of Medicine, 2Neurology Department, Pontificia Universidad Javeriana
Objective:
To synthesize current evidence on the clinical presentation and neuroimaging characteristics of limbic-predominant age-related TDP-43 encephalopathy (LATE), emphasizing its differentiation from Alzheimer’s disease (AD) and other late-life neurodegenerative disorders.
Background:
LATE is an emerging cause of cognitive decline in older adults, linked to TDP-43 pathology that predominantly affects the hippocampus and amygdala. Its clinical picture often resembles AD, contributing to diagnostic uncertainty and underrecognition in everyday practice. Defining its characteristic clinical and imaging patterns is essential to improve diagnostic precision, patient counseling, and interpretation of biomarker data.
Design/Methods:
A narrative review of the literature was performed using PubMed and Scopus databases. Studies published addressing clinical manifestations, imaging correlates, neuropathological staging, and biomarker differentiation of LATE from AD and frontotemporal lobar degeneration were identified and analyzed. Reported patterns of hippocampal asymmetry, amygdalar involvement, and cortical atrophy distribution were synthesized into a diagnostic framework.
Results:
LATE commonly presents as an amnestic syndrome with slower progression, later onset, and prominent hippocampal and amygdalar atrophy, often asymmetric, on MRI. Compared with AD, cortical involvement is initially limited. Co-pathology with AD is frequent, producing mixed phenotypes characterized by accelerated cognitive decline. Emerging PET tracers and advanced MRI techniques may enable in-vivo detection of TDP-43–related neurodegeneration, although no validated biomarker is currently available.
Conclusions:
LATE represents a distinct and clinically meaningful neuropathological entity that remains frequently misclassified as AD. Recognizing its imaging and clinical signatures can enhance diagnostic accuracy in older adults and inform the development of targeted diagnostic and biomarker strategies.
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