Skip to Content
Merck
  • In Vivo Chimeric Alzheimer's Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons.

In Vivo Chimeric Alzheimer's Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons.

Cell reports (2020-07-30)
Ramsey Najm, Kelly A Zalocusky, Misha Zilberter, Seo Yeon Yoon, Yanxia Hao, Nicole Koutsodendris, Maxine Nelson, Antara Rao, Alice Taubes, Emily A Jones, Yadong Huang
ABSTRACT

Despite its clear impact on Alzheimer's disease (AD) risk, apolipoprotein (apo) E4's contributions to AD etiology remain poorly understood. Progress in answering this and other questions in AD research has been limited by an inability to model human-specific phenotypes in an in vivo environment. Here we transplant human induced pluripotent stem cell (hiPSC)-derived neurons carrying normal apoE3 or pathogenic apoE4 into human apoE3 or apoE4 knockin mouse hippocampi, enabling us to disentangle the effects of apoE4 produced in human neurons and in the brain environment. Using single-nucleus RNA sequencing (snRNA-seq), we identify key transcriptional changes specific to human neuron subtypes in response to endogenous or exogenous apoE4. We also find that Aβ from transplanted human neurons forms plaque-like aggregates, with differences in localization and interaction with microglia depending on the transplant and host apoE genotype. These findings highlight the power of in vivo chimeric disease modeling for studying AD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-TRA-1-81 Antibody, clone TRA-1-81, clone TRA-1-81, Chemicon®, from mouse
Sigma-Aldrich
Anti-GABA antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Pax6 Antibody, clone AD1.5, ascites fluid, clone AD1.5, Chemicon®
Sigma-Aldrich
Anti-NeuN Antibody, serum, from guinea pig
Sigma-Aldrich
Anti-Nuclei Antibody, clone 235-1, clone 235-1, Chemicon®, from mouse
Millipore
Accutase cell detachment solution, A cell detachment solution of proteolytic & collagenolytic enzymes. The reagent is useful for creating single cell suspensions from clumped cell cultures for accurate cell counting, detachment of cells from primary tissue.
Sigma-Aldrich
Anti-TRA-1-60 Antibody, clone TRA-1-60, clone TRA-1-60, Chemicon®, from mouse
Sigma-Aldrich
Anti-Vesicular Glutamate Transporter 1 Antibody, clone 3C10.2, Chemicon®, from mouse