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

Topic: Brain proteins, microglia and lab models

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) (Table 1). Multivariate analysis confirmed associations between HS and 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% among cognitively impaired individuals (n = 432) (Table 3). Among individuals with HS but no TDP-43 pathology (n = 21), 48.4% had Braak-AD stage ≥3, and 64.5% exhibited arteriolosclerosis. HS is relatively uncommon in this population-based brain bank but is strongly associated with TDP-43 pathology. However, vascular pathology also plays a significant role, particularly in populations with high cardiovascular risk. This limits its predictive value for LATE-NC, even among cognitively impaired individuals. Given the absence of an in vivo biomarker for LATE-NC, further research is needed to determine whether MRI-detectable HS can serve as a reliable surrogate marker for LATE-NC pathology, particularly in genetically diverse populations with multiple comorbidities.

@article{paes2025-41499176,
  author  = {Paes, Vítor Ribeiro and Justo, Alberto Fernando Oliveira and Silva, Caroline Matos and Rodriguez, Roberta and Leite, Renata Elaine Paraízo and Suemoto, Cláudia Kimie and Pasqualucci, Carlos Augusto and Ferriolli, Eduardo and others},
  title   = {{Bridging the Gap: Can Hippocampal Sclerosis Serve as a Surrogate Biomarker for LATE‐NC?}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70856_107174},
  pmid    = {41499176},
  url     = {https://doi.org/10.1002/alz70856_107174}
}

Key findings

• 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) (Table 1).
• Multivariate analysis confirmed associations between HS and 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% among cognitively impaired individuals (n = 432) (Table 3).

Why it matters

In a brain bank of 1,307 individuals, hippocampal sclerosis was strongly associated with TDP-43 pathology, but its positive predictive value for TDP-43 pathology was only 48.8%, rising to 59.4% among cognitively impaired individuals, and vascular pathology also played a significant role. The authors conclude this limits its predictive value for LATE-NC and call for further research, so it does not provide a treatment, cure or prevention.

Study details

• Participants432
• Effect size36.9%; 49.7%; 3.1%
• Evidence strengthLow

Read the original

• DOI: 10.1002/alz70856_107174
• PubMed: 41499176
• Original source →
• Free full text: Alzheimer s & Dementia →

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