Somatic copy number variant load in neurons of healthy controls and Alzheimer's disease patients

Zeliha Gözde Turan, Vincent Richter, Jana Bochmann, Poorya Parvizi, Etka Yapar, Ulas Işıldak, Sarah-Kristin Waterholter, Sabrina Leclere-Turbant, Çağdaş Devrim Son, Charles Duyckaerts, İdil Yet, Thomas Arendt, Mehmet Somel, Uwe Ueberham

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The possible role of somatic copy number variations (CNVs) in Alzheimer's disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using low-coverage scWGS on pyramidal neurons dissected via both laser capture microdissection (LCM) and fluorescence activated cell sorting (FACS) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum. Among reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. On the technical aspects, we observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with FACS. To reduce within-cell read depth variation, we proposed a principal component analysis-based denoising approach that significantly improves signal-to-noise ratios. Lastly, we showed that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons.

Original languageEnglish
Article number175
Pages (from-to)175
JournalActa Neuropathologica Communications
Issue number1
Publication statusPublished - 30 Nov 2022

Keywords / Materials (for Non-textual outputs)

  • Alzheimer’s disease
  • Brain
  • Copy number variation
  • Denoising
  • Fluorescence-activated cell sorting
  • Laser capture microdissection
  • Single-cell whole-genome sequencing


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