Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer's disease, Down syndrome, and Parkinson's disease

Topic: Brain proteins, microglia and lab models

Abstract Extensive evidence suggests overlapping pathological mechanisms in the brain of individuals with Parkinson´s disease dementia, Down syndrome dementia, and Alzheimer´s disease. For these neurodegenerative dementias, we observed that the chronological age did not align with their biological age, which was determined based on hippocampal transcript levels (i.e., transcriptional age). Subsequently, we performed a transcriptomic analysis that corrected for the transcriptional age in the hippocampus of affected individuals, highlighting common underlying pathogenic mechanisms.

Key findings

• For these neurodegenerative dementias, we observed that the chronological age did not align with their biological age, which was determined based on hippocampal transcript levels (i.e., transcriptional age).
• Subsequently, we performed a transcriptomic analysis that corrected for the transcriptional age in the hippocampus of affected individuals, highlighting common underlying pathogenic mechanisms.
• There were 45 common differentially expressed genes (DEGs), whereas enriched functional terms were related to lysine N-methyltransferase activity and intermediate filament.
• Co-expression network analysis displayed a module that was significantly downregulated in the non-demented control group only.

Why it matters

This transcriptomic study of hippocampus tissue found that chronological age did not match biological age in Parkinson's disease dementia, Down syndrome dementia, and Alzheimer's disease, and identified 45 common differentially expressed genes. It highlights shared mechanisms but tests no treatment or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.21203/rs.3.rs-7703742/v1
• Original source →

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@article{crans2025-7fc8ca4a,
  author  = {Crans, R. A. J. and Fructuoso, M. and Cardozo, K. B. and Recaioglu, H. and Fonseca, J. S. and Vermeiren, Y. and Strydom, A. and Dam, D. V. and others},
  title   = {{Common pathogenic mechanisms in the hippocampus across neurodegenerative dementias: Alzheimer's disease, Down syndrome, and Parkinson's disease}},
  journal = {NPJ dementia},
  year    = {2025},
  doi     = {10.21203/rs.3.rs-7703742/v1},
  url     = {https://doi.org/10.21203/rs.3.rs-7703742/v1}
}

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