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

TY - JOUR

T1 - Predicting progression to Alzheimer’s disease with human hippocampal progenitors exposed to serum

AU - Maruszak, Aleksandra

AU - Lee, Hyunah

AU - Silajdzic, Edina

AU - Murphy, Tytus

AU - Liu, Benjamine

AU - Shi, Liu

AU - De Lucia, Chiara

AU - Douiri, Abdel

AU - Salta, Evgenia

AU - Nevado-Holgado, Alejo J.

AU - Teunissen, Charlotte E.

AU - Jelle Visser, Pieter

AU - Price, Jack

AU - Zetterberg, Henrik

AU - Lovestone, Simon

AU - Thuret, Sandrine

PY - 2022/11/11

Y1 - 2022/11/11

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - prognostic biomarker

KW - neurogenesis

KW - hippocampal progenitors

U2 - 10.1093/brain/awac472

DO - 10.1093/brain/awac472

M3 - Article

SN - 0006-8950

JO - Brain

JF - Brain

ER -