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Cellular Phenotyping of Hippocampal Progenitors Exposed to Patient Serum Predicts Progression to Alzheimer's Disease

73 Pages Posted: 30 Sep 2019 Sneak Peek Status: Review Complete

See all articles by Aleksandra Maruszak

Aleksandra Maruszak

King’s College London - Department of Basic and Clinical Neuroscience

Tytus Murphy

King’s College London - Department of Basic and Clinical Neuroscience

Benjamine Liu

University of Oxford - Department of Psychiatry

Chiara De Lucia

King’s College London - Department of Basic and Clinical Neuroscience

Abdel Douiri

King’s College London - Department of Public Health Sciences

Alejo J. Nevado

University of Oxford - Department of Psychiatry

Charlotte E. Teunissen

VU University Medical Center - Amsterdam Neuroscience

Pieter J. Visser

Maastricht University

Jack Price

King’s College London - Department of Basic and Clinical Neuroscience

Simon Lovestone

University of Oxford - Department of Psychiatry

Sandrine Thuret

King’s College London - Department of Basic and Clinical Neuroscience

More...

Abstract

The generation of neurons persists into adulthood in the human hippocampus and is modulated by the circulatory systemic environment. Hippocampal neurogenesis is important for learning and memory and altered early in Alzheimer’s Disease (AD). Evaluating hippocampal neurogenic processes during AD progression could therefore be a biomarker for early disease detection. Here, we used a human hippocampal progenitor cell line to evaluate in vitro over time the neurogenic impact of the systemic milieu (i.e. serum) of individuals with mild cognitive impairment (MCI) as they either progressed to AD or remained stable. Cellular phenotyping and linear mixed effects models for repeated measures revealed that decreased proliferation, increased cell death and neurogenesis characterized progression from MCI to AD. Using stepwise logistic regression and machine learning we show that these baseline cellular readouts are significant predictors of progression from MCI to AD.

Keywords: Hippocampal neurogenesis, human hippocampal progenitor cells, Stem cells, serum, Alzheimer's Disease, Mild Cognitive Impairment, biomarker

Suggested Citation

Maruszak, Aleksandra and Murphy, Tytus and Liu, Benjamine and De Lucia, Chiara and Douiri, Abdel and Nevado, Alejo J. and Teunissen, Charlotte E. and Visser, Pieter J. and Price, Jack and Lovestone, Simon and Thuret, Sandrine, Cellular Phenotyping of Hippocampal Progenitors Exposed to Patient Serum Predicts Progression to Alzheimer's Disease (September 25, 2019). CELL-STEM-CELL-D-19-00646. Available at SSRN: https://ssrn.com/abstract=3459560 or http://dx.doi.org/10.2139/ssrn.3459560
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Aleksandra Maruszak

King’s College London - Department of Basic and Clinical Neuroscience ( email )

Strand
London, England WC2R 2LS
United Kingdom

Tytus Murphy

King’s College London - Department of Basic and Clinical Neuroscience ( email )

Strand
London, England WC2R 2LS
United Kingdom

Benjamine Liu

University of Oxford - Department of Psychiatry

Warneford Hospital
Warneford Ln
Oxford, OX3 7JX
United Kingdom

Chiara De Lucia

King’s College London - Department of Basic and Clinical Neuroscience ( email )

Strand
London, England WC2R 2LS
United Kingdom

Abdel Douiri

King’s College London - Department of Public Health Sciences ( email )

5th Floor Capital House
42 Weston Street
London, SE1 3QD
United Kingdom

Alejo J. Nevado

University of Oxford - Department of Psychiatry ( email )

Warneford Hospital
Warneford Ln
Oxford, OX3 7JX
United Kingdom

Charlotte E. Teunissen

VU University Medical Center - Amsterdam Neuroscience

Amsterdam
Netherlands

Pieter J. Visser

Maastricht University ( email )

P.O. Box 616
Maastricht, 6200MD
Netherlands

Jack Price

King’s College London - Department of Basic and Clinical Neuroscience

Strand
London, England WC2R 2LS
United Kingdom

Simon Lovestone

University of Oxford - Department of Psychiatry

Warneford Hospital
Warneford Ln
Oxford, OX3 7JX
United Kingdom

Sandrine Thuret (Contact Author)

King’s College London - Department of Basic and Clinical Neuroscience ( email )

Strand
London, England WC2R 2LS
United Kingdom

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