Bridging the Gap: Can Hippocampal Sclerosis Serve as a Surrogate Biomarker for LATE-NC?

Q: What is the study’s central question about hippocampal sclerosis (HS)?

Whether MRI-detectable HS can serve as a reliable surrogate biomarker for underlying LATE-NC pathology.

Q: What were the key findings regarding HS and LATE-NC?

HS was uncommon (3.1%) but showed significant multivariate associations with LATE-NC (p < 0.001). HS was also linked to lacunar infarcts and vascular pathology, which reduced its predictive value for LATE-NC.

Sep 30, 2026

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Background: Hippocampal sclerosis (HS) involves neuronal loss and gliosis in CA regions and is linked to epilepsy, hypoxia, and neurodegenerative disease. In dementia, HS is increasingly considered a biomarker candidate for Limbic-predominant Age-related TDP-43 Encephalopathy neuropathological change (LATE-NC), yet LATE-NC lacks a validated in vivo biomarker. Since HS is MRI-detectable, the study evaluates HS prevalence and pathological associations for LATE-NC. Methods: Data from BAS-GEROLAB in São Paulo applied CDR-based clinical information and morphological, vascular, and immunohistochemical assessments for beta-amyloid, tau, alpha-synuclein, and TDP-43; epilepsy history was excluded. Results and conclusion assess HS as a surrogate marker.

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DOI: 10. 1002/alz70856_107174 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Bridging the Gap: Can Hippocampal Sclerosis Serve as a Surrogate Biomarker for LATE-NC? Vitor Ribeiro Paes1 Alberto Fernando Oliveira Justo 1 Caroline Matos Silva2 Roberta Rodriguez3 Renata Elaine Paraizo Leite4 Claudia Kimie Suemoto5 Carlos Augusto Pasqualucci6 Eduardo Ferriolli7 Wilson Jacob-Filho5 Lea T. Grinberg4, 8 1 Physiopathology in Aging Laboratory (LIM-22), University of Sao Paulo Medical School, São Paulo, São Paulo, Brazil 2 Physiopathology in Aging Laboratory (LIM-22), University of São Paulo Medical School, São Paulo, Brazil 3 LIM44, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil 4 Biobank forAging Studies of the University of São Paulo, São Paulo, São Paulo, Brazil 5 Division of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, São Paulo, São Paulo, Brazil 6 Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 7 University of Sao Paulo Medical School, São Paulo, Brazil 8 Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA Correspondence Vitor Ribeiro Paes, Physiopathology in Aging Laboratory (LIM-22), University of Sao Paulo Medical School, São Paulo, São Paulo, Brazil. [Email:](Email: vitor.rpaes@hc.fm.usp.br)[ vitor.rpaes@hc.fm.usp.br](Email: vitor.rpaes@hc.fm.usp.br) Abstract Background: Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosisin the cornu Ammonis (CA) region of the hippocampus and is associated with epilepsy, hypoxia, and neurodegenerative diseases. In dementia, HS is increasingly recognized as a potential biomarker for Limbic-predominant Age-related TDP-43 Encephalopathy neuropathological change (LATE-NC). However, LATE-NC currently lacks a validated in vivo biomarker. Since HS is detectable by MRI, a key question is whether HS could serve as a reliable proxy for underlying LATE-NC pathology. This study examines the prevalence and pathological associations of HS across neurodegenerative diseases in a large population-based brain bank to assess its potential as a biomarker for LATE-NC. Method: Data were analyzed from the Biobank for Aging Study (BAS-GEROLAB) in São Paulo, Brazil. Clinical and epidemiological information was obtained from next of kin using validated protocols, including the Clinical Dementia Rating (CDR) scale. Neuropathological assessments included morphological, vascular, and immunohistochemical analyses for beta-amyloid, tau, alpha-synuclein, and TDP-43. HS was defined as ≥70% neuronal loss in CA1 (unilateral). Individuals with a history of epilepsy were excluded. Result: Among 1,307 individuals, 36. 9% were non-White and 49.7% were women. HS was identified in 41 participants (3.1%), with higher prevalence among older individuals, women, and those with lower education levels (p < 0.001). HS was also significantly associated with hyaline arteriolosclerosis (p = 0.001) and diabetes mellitus(p = 0.003)(Table1). Multivariate analysis confirmed associations between HSand LATE-NC (p < 0.001) as well as lacunar infarcts (p = 0.031) (Table 2). The positive predictive value (PPV) of HS for TDP-43 pathology was 48.8%, increasing to 59.4% This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e107174. [https://doi.org/10.1002/alz70856_107174](https://doi.org/10.1002/alz70856_107174) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of3 BIOMARKERS among cognitively impaired individuals (n = 432) (Tab

FAQs

What is the study’s central question about hippocampal sclerosis (HS)?

Whether MRI-detectable HS can serve as a reliable surrogate biomarker for underlying LATE-NC pathology.

How was HS defined and how were participants selected?

HS was defined as ≥70% neuronal loss in CA1 (unilateral). Individuals with a history of epilepsy were excluded, and clinical information used validated protocols including the CDR scale.

What were the key findings regarding HS and LATE-NC?

HS was uncommon (3.1%) but showed significant multivariate associations with LATE-NC (p < 0.001). HS was also linked to lacunar infarcts and vascular pathology, which reduced its predictive value for LATE-NC.

Sep 30, 2026

Uploaded by Cipher