Human brain aging heterogeneity observed from multi-region omics data reveals a subtype closely related to Alzheimer's disease
Peng, S.; Wang, E.; Wang, M.; Wang, X.; Yu, K.; Fu, Y.; Poudel, S.; Ho, L.; Narayan, S.; Huffman, D.; Gaiteri, C.; Bennett, D. A.; Ehrlich, M. E.; Haroutunian, V.; Peng, J.; Zhang, B.; Tu, Z.
Show abstract
INTRODUCTION: The interconnection between brain aging and Alzheimers disease (AD) remain to be elucidated. METHODS: We investigated multi-omics (transcriptomics and proteomics) data from multiple brain regions (i.e., the hippocampus (HIPP), prefrontal cortex (PFC), and cerebellum (CRBL)) in cognitively normal individuals. RESULTS: We found that brain samples could be divided into ADL (AD-like) and NL (normal) subtypes which were correlated across brain regions. The differentially expressed genes in the ADL samples highly overlapped with AD gene signatures and the changes were consistent across brain regions (PFC and HIPP) in the multi-omics data. Intriguingly, the ADL subtype in PFC showed more differentially expressed genes than other brain regions, which could be explained by the baseline gene expression differences in the PFC NL samples. DISCUSSION: We conclude that brain aging heterogeneity widely exists, and our findings corroborate with the hypothesis that AD-related changes occur decades before the clinical manifestation of cognitive impairment in a sub-population.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Gene module-trait network analysis uncovers cell type specific systems and genes relevant to Alzheimers Disease 95%
- Interpretable deep learning of myelin histopathology in age-related cognitive impairment 95%
- Circular RNA detection identifies circPSEN1 alterations in brain specific to Autosomal Dominant Alzheimer Disease 95%
Similar papers in this journal
- A meta-analysis of brain DNA methylation across sex, age and Alzheimer’s disease points for accelerated epigenetic aging in neurodegeneration 95%
- Biological and Disease Hallmarks of Alzheimer’s Disease Defined by Alzheimer’s Disease Genes 93%
- Genetic background influences the 5XFAD Alzheimer's disease mouse model brain proteome 93%
Similar papers in this journal
- Complementary value of molecular, phenotypic and functional aging biomarkers in dementia prediction 95%
- Inter- and intra-chromosomal modulators of the APOE ε2 and ε4 effects on the Alzheimer’s disease risk 94%
- Complex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci 94%
Similar papers in this journal
- Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment 95%
- Polygenic effects on the risk of Alzheimer’s disease in the Japanese population 94%
- Age, Sex and Alzheimer's disease: A longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer's patients 94%