bioRxivNeurosciencePreprint
Geometric Fragility in Alzheimer's Disease: Probing the Loss of Hippocampal Hierarchical Abstraction via Contrastive Point Cloud Modeling
Yiquan WangiD, Yuhan Chang, Jialin Zhang, Minnuo CaiiD, Jiayao YaniD, Hongtian Zhao, the Frontotemporal Lobar Degeneration Neuroimaging Initiative
Abstract
While human spatial cognition relies on hierarchical abstraction to integrate local features, Alzheimers disease (AD) pathology is often reduced to local volumetric atrophy. We propose geometric fragility as a distinct failure of global topological integrity within the hippocampus rather than a mere accumulation of local errors. Using a texture-invariant point cloud framework, we contrasted local feature aggregation with global hierarchical attention as computational probes for structural perception. The global paradigm demonstrated enhanced diagnostic sensitivity and exhibited cognitive resilience under simulated neuronal sparsity by maintaining structural recognition where local models suffered pattern collapse. Global modeling effectively unfolded the pathological manifold, revealing a linear trajectory of geometric degradation consistently correlated with clinical cognitive decline. These findings indicate that AD progression may be characterized as a systemic topological dissolution and suggest that effective biomarkers should prioritize hierarchical shape abstraction to accurately map the continuous transition from healthy cognition to dementia.
- organism: human
- assay: spatial transcriptomics
- research focus: cell type annotation
- research focus: dimensionality reduction
- research focus: trajectory inference
- approach: contrastive learning
- Citations
- 0
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Hippocampal grey matter changes across scales in Alzheimer's Disease
Bradley G. Karat, Mahdieh Varvani Farahani, … Alzheimer’s Disease Neuroimaging Initiative·bioRxiv·Oct 15, 2025
- Multimodal Hippocampal Subfield Grading For Alzheimer’s Disease Classification
Kilian Hett, Vinh‐Thong Ta, … Randall Griffith·Scientific ReportsPeer-reviewed·Sep 25, 2019
- Dissociation between impaired explicit spatial remapping and preserved implicit neural dynamics in Alzheimers disease
Xueling Wang, Yimeng Wang, … Chenguang Zheng·bioRxiv·Jul 9, 2026
- Amyloid-Induced Network Resilience and Collapse in Alzheimer's Disease: Insights from Computational Modeling
Ediline L. F. Nguessap, Damien Depannemaecker, Fernando F. Ferreira·bioRxiv·Feb 11, 2026
- CA1 and CA3 pyramidal cell morphologies under Alzheimer’s disease Amyloid beta interaction
Yuri Elias Rodrigues, Josiane da Silva Freitas·bioRxiv·Sep 12, 2017
- Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer disease
Jiaxin Cindy Tu, Peter R Millar, … The Dominantly Inherited Alzheimer Network (DIAN)·Network NeurosciencePeer-reviewed·Jan 1, 2024