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

Aleksandra Maruszak; Edina Silajdžić; Hyunah Lee; Tytus Murphy; Benjamine Liu; Liu Shi; Chiara de Lucia; Abdel Douiri; Evgenia Salta; Alejo J Nevado; Charlotte E Teunissen; Pieter J Visser; Jack Price; Henrik Zetterberg; Simon Lovestone; Sandrine Thuret

doi:10.1093/brain/awac472

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

Brain. 2023 May 2;146(5):2045-2058. doi: 10.1093/brain/awac472.

Authors

Aleksandra Maruszak¹, Edina Silajdžić¹, Hyunah Lee¹, Tytus Murphy¹, Benjamine Liu², Liu Shi², Chiara de Lucia¹, Abdel Douiri³, Evgenia Salta^{4

5}, Alejo J Nevado², Charlotte E Teunissen⁵, Pieter J Visser^{6

7}, Jack Price¹, Henrik Zetterberg^{8

9

10

11}, Simon Lovestone^{2

12}, Sandrine Thuret¹

Affiliations

¹ Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology & Neuroscience, King's College London, London, SE5 9RX, UK.
² Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.
³ Department of Population Health Sciences, King's College London, London, SE1 1UL, UK.
⁴ Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.
⁵ Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
⁶ Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands.
⁷ Department of Neurology, Alzheimer Center, VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden.
⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
¹⁰ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.
¹¹ UK Dementia Research Institute at UCL, London, WC1E 6BT, UK.
¹² Janssen Medical UK, B-2340 Beerse, Belgium.

Abstract

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer's disease. As hippocampal neurogenesis is modulated by the circulatory systemic environment, evaluating a proxy of how hippocampal neurogenesis 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 hippocampal neurogenesis. A human hippocampal progenitor cell line was treated with longitudinal serum samples from individuals with mild cognitive impairment, who either progressed to Alzheimer's disease or remained cognitively stable. Mild cognitive impairment to Alzheimer's disease progression was characterized 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.

Keywords: Alzheimer’s disease; hippocampal progenitors; neurogenesis; prognostic biomarker.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alzheimer Disease* / metabolism
Cognitive Dysfunction* / psychology
Disease Progression
Hippocampus / metabolism
Humans
Learning
Neurogenesis / physiology

Grants and funding

MC_PC_18052/Medical Research Council/United Kingdom