Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum

Aleksandra Maruszak, Hyunah Lee, Edina Silajdzic, Tytus Murphy, Benjamine Liu, Liu Shi, Chiara De Lucia, Abdel Douiri, Evgenia Salta, Alejo J. Nevado-Holgado, Charlotte E. Teunissen, Pieter Jelle Visser, Jack Price, Henrik Zetterberg, Simon Lovestone, Sandrine Thuret

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Abstract

Adult hippocampal neurogenesis (HN) is important for learning and memory and is altered early in Alzheimer’s disease. Since HN is modulated by the circulatory systemic environment, evaluating a proxy of how HN is affected by the systemic milieu could serve as an early biomarker for Alzheimer’s disease progression. Here, we used an in vitro assay to model the impact of systemic environment on HN. A human hippocampal progenitor cell line was treated with longitudinal serum samples from individuals with mild cognitive impairment (MCI), who either progressed to Alzheimer’s disease or remained cognitively stable. MCI to Alzheimer’s disease progression was characterised most prominently with decreased proliferation, increased cell death, and increased neurogenesis. A subset of ‘baseline’ cellular readouts together with education level were able to predict Alzheimer’s disease progression. The assay could provide a powerful platform for early prognosis, monitoring disease progression, and further mechanistic studies.
Original languageEnglish
JournalBrain
DOIs
Publication statusAccepted/In press - 11 Nov 2022

Keywords

  • Alzheimer’s disease
  • prognostic biomarker
  • neurogenesis
  • hippocampal progenitors

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