ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
A brain-derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Asymptomatic Versus Symptomatic Alzheimer's Disease Neuropathology: A Systematic Review of Differences Reported in Post-Mortem Studies.Neuropathology and applied neurobiology · 2026Pooled it
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Vitamin B6 Modifies Tau-Induced Cellular Stress- and Proteostasis-Related Responses.Journal of fungi (Basel, Switzerland) · 2026Article
- A brain-derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
introductionMisfolded tau can assemble into oligomers that adopt distinct conformations, referred to as polymorphs, each with unique biochemical and pathological properties. These tau polymorphs are thought to influence disease progression in Alzheimer's disease (AD) and related disorders. Interestingly, some individuals with AD pathology remain cognitively intact (non-demented with Alzheimer's neuropathology [NDAN]), suggesting potential differences in tau polymorph profiles.
methodsBrain-derived tau oligomers (BDTOs) were isolated from post mortem hippocampi of AD and NDAN individuals. Their biophysical, biochemical, and functional properties were assessed via protease digestion, immunocharacterization, atomic force microscopy, tau seeding in biosensor cells, hippocampal slice electrophysiology, and SH-SY5Y toxicity assays.
resultsNDAN-BDTOs exhibited protease resistance, different conformational profiles, formed larger aggregates, preserved synaptic function, and reduced neuronal toxicity compared to AD-BDTOs. DISCUSSION: The data suggests that a structurally stable yet less toxic tau polymorph in NDAN may underlie cognitive resilience, supporting the therapeutic relevance of targeting specific tau polymorphs. HIGHLIGHTS: Non-demented with Alzheimer's neuropathology (NDAN) brain-derived tau oligomers (BDTOs) exhibit distinct, more stable structural polymorphs compared to those from Alzheimer's disease (AD). NDAN-BDTOs are larger, more protease resistant, and less toxic in cell and hippocampal slice models. Both NDAN- and AD-BDTOs seed tau aggregation, but NDAN-BDTOs promote formation of less toxic assemblies. Structural stability of NDAN-BDTOs may contribute to cognitive resilience despite AD pathology. Mimicking non-toxic tau polymorphs could represent a novel therapeutic strategy for AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.