Session Information
Date: Wednesday, June 22, 2016
Session Title: Cognitive disorders
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To model Dementia with Lewy bodies (DLB) using neurons derived from patients clinically diagnosed with the disease.
Background: A major challenge in neurodegenerative disease research has been the unavailability of living, diseased neurons. This barrier was recently overcome by using fibroblasts from living patients and reprogramming them into neurons via induced pluripotent stem cells (iPSCs) that can be directed towards a neural fate, or directly as induced neurons (iNs), bypassing the stem cell stage. Direct reprogramming is both time-advantageous and has been shown to preserve epigenetic marks resulting from aging, a particularly useful feature in terms of modeling age-related diseases. While the related Parkinson’s and Alzheimer’s diseases have been studied using this methodology, DLB has received less attention.
Methods: We have obtained fibroblasts from five clinically diagnosed DLB patients through the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (ADRC). We also have fibroblasts from two unaffected first-degree relatives to use as genetic controls, and three unrelated, non-demented age-matched controls. The reprogramming procedures were conducted based on existing methods, and derived neurons were matured for several weeks, some in co-culture with astrocytes.
Results: We have successfully reprogrammed DLB patient fibroblasts to iPSCs and iNs. The neurons we generated display many neuronal features, including the expression of neuronal markers, as verified by immunohistochemistry. We have done RNA-sequencing to examine differential gene expression between patient lines and controls, and are now optimizing functional assays based on these findings.
Conclusions: As evidenced by our preliminary results, we suspect the iPSC/iN approach to be promising in the context of DLB, in order to further our understanding of the mechanisms underlying the disease.
To cite this abstract in AMA style:
D.H. Adamowicz, J. Mertens, D.P. Salmon, D.R. Galasko, S. Roy, F.H. Gage. Modeling dementia with Lewy bodies using patient-derived neurons [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/modeling-dementia-with-lewy-bodies-using-patient-derived-neurons/. Accessed May 24, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/modeling-dementia-with-lewy-bodies-using-patient-derived-neurons/