Modeling Late-Onset Sporadic Alzheimer’s Disease Using Patient-Derived Cells: A Review

TL;DR

This paper reviews how patient-derived cells can be used to model late-onset Alzheimer’s disease, focusing on neurons and comparing two cell reprogramming methods.

Contribution

The paper provides a comparative analysis of two reprogramming methods for generating Alzheimer’s disease patient neurons.

Findings

Induced pluripotent stem cells and induced neurons are used to model late-onset Alzheimer’s disease.

These models can recapitulate cellular and molecular pathologies seen in Alzheimer’s patient brains.

LOAD models are essential for understanding the disease’s origin and pathophysiology.

Abstract

Late-onset sporadic Alzheimer’s disease (LOAD) is the most common form of dementia. The disease is characterized by progressive loss of memory and behavioral changes followed by neurodegeneration of all cortical areas. While the contribution of genetic and environmental factors is important, advanced aging remains the most important disease risk factor. Because LOAD does not naturally occur in most animal species, except humans, studies have traditionally relied on the use of transgenic mouse models recapitulating early-onset familial Alzheimer’s disease (EOAD). Hence, the development of more representative LOAD models through reprograming of patient-derived cells into neuronal, glial, and immune cells became a necessity to better understand the disease’s origin and pathophysiology. Herein, and focusing on neurons, we review current work in the field and compare results obtained with two different reprograming methods to generate LOAD patient’s neuronal cells: the induced pluripotent stem cell and induced neuron technologies. We also evaluate if these models can faithfully mimic cellular and molecular pathologies observed in LOAD patients’ brains.

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