Alzheimer's Imaging Consortium.

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Biomarker Discovery

Background:

• Hippocampal sclerosis (HS) involves neuronal loss and gliosis, linked to epilepsy, hypoxia, and neurodegeneration.
• HS is a potential biomarker for Limbic-predominant Age-related TDP-43 Encephalopathy neuropathological change (LATE-NC) in dementia.
• Currently, LATE-NC lacks a validated in vivo biomarker, prompting investigation into MRI-detectable HS as a proxy.

Purpose of the Study:

• To examine the prevalence and pathological associations of HS in a large population-based brain bank.
• To assess the potential of HS as a reliable biomarker for LATE-NC.
• To evaluate the influence of vascular pathology on HS as a LATE-NC biomarker.

Main Methods:

• Analysis of data from the Biobank for Aging Study (BAS-GEROLAB).
• Clinical and epidemiological data collection via validated protocols.
• Neuropathological assessments including immunohistochemistry for TDP-43 and other markers; HS defined as ≥70% neuronal loss in CA1.

Main Results:

• HS prevalence was 3.1%, higher in older individuals, women, and those with lower education.
• HS was associated with hyaline arteriolosclerosis, diabetes mellitus, and LATE-NC.
• The positive predictive value of HS for TDP-43 pathology was 48.8%, increasing to 59.4% in cognitively impaired individuals.

Conclusions:

• HS is associated with TDP-43 pathology but also significantly influenced by vascular factors.
• Vascular pathology limits the predictive value of HS for LATE-NC, especially in high cardiovascular risk populations.
• Further research is required to validate MRI-detectable HS as a surrogate marker for LATE-NC, particularly in diverse populations.