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Transcriptomic Profiling of Sporadic Alzheimer’s Disease Patients

  • Author(s): Anantharaman, Balaji Ganesh
  • Advisor(s): Subramaniam, Shankar
  • et al.
No data is associated with this publication.
Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized physically by dementia and physiologically by senile plaques and neurofibrillary tangles in the brain. Mutations to the genes PSEN1, PSEN2 and APP result in the manifestation of the dominantly inherited form of AD, Familial AD. Though a number of risk factors, including genetic mutations, environmental factors, and aging, have been attributed to the sporadic form of AD, the underlying mechanistic basis of the disease is yet to be unearthed. Analysing sporadic AD RNA-seq samples together with non-demented controls allows us to uncover these molecular mechanisms and to this end, we have analysed a 50-sample RNA-Seq dataset, with 40 AD samples and 10 controls, and identified disease-associated endotypes that arise from gene expression changes between the AD cases and the controls. We have also described an adapted framework for analysing low-quality RNA-seq samples (RIN > 1, < 3), and applying this framework to our data results in the categorization of the samples into two groups which show different degrees of differential expression with respect to the controls. Endotypes such as Dedifferentiation and Synaptic Signalling are preferentially enriched in samples from one group, although a small subset of samples from this group exhibits a significantly higher enrichment of said endotypes compared to other group members. We hypothesize that these differences in endotype signatures manifest due to varying severity among the samples, and scrutinizing the similarities and dissimilarities among the groups can provide insights into the etiology of Sporadic AD.

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This item is under embargo until January 7, 2023.