Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): Clinical and Neuropathological Associations

• Published in: Journal of neuropathology and experimental neurology 2020-03, Vol.79 (3), p.305-313
• Main Authors: Besser, Lilah M, Teylan, Merilee A, Nelson, Peter T
• Format: Article
• Language: English
• Subjects: Age factors in disease; Aged, 80 and over; Brain - pathology; Brain research; Clinical pathology; Diagnosis; DNA binding proteins; Encephalopathy; Female; Health aspects; Humans; Limbic System - pathology; Male; Neuropathology; Original; Risk Factors; TDP-43 Proteinopathies - complications; TDP-43 Proteinopathies - diagnosis; TDP-43 Proteinopathies - pathology; Terminology
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/nlz126

Abstract Recently, a consensus working group provided new terminology for a common disease entity, limbic predominant age-related TDP-43 encephalopathy (LATE), and its neuropathological substrate (LATE-NC). LATE-NC not only often co-occurs with Alzheimer disease neuropathological change (ADNC), but also may present in isolation. The present study aimed to investigate potential risk factors and neuropathological characteristics associated with LATE-NC. A sample of 616 autopsied participants (>75 years at death), with TDP-43 immunohistochemical studies performed, was obtained from the National Alzheimer’s Coordinating Center. Logistic regression analyses examined associations between demographic, clinical and neuropathological characteristics and LATE-NC (TDP-43 in amygdala, hippocampus, or entorhinal/inferior temporal cortex) (alpha = 0.05). Adjusted models indicated that ADNC, hippocampal sclerosis (HS), arteriolosclerosis, and limbic or amygdala-predominant Lewy body disease (LBD), but not other LBD subtypes, were associated with higher odds of LATE-NC, whereas congestive heart failure (CHF) and motor problems as first predominant symptom were associated with lower odds of LATE-NC. Our findings corroborate previous studies indicating associations between LATE-NC and ADNC, HS, and arteriolosclerosis. Novel findings suggest the association with LATE-NC is restricted to amygdala/limbic-predominant subtype of LBD, and a possible protective (or competing risk) association with CHF. This study may inform future hypothesis-driven research on LATE-NC, a common brain disease of aging.