Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability

• DOI: 10.1016/j.stemcr.2017.10.015
• Publication Date: 2017-11-16T20:03:59Z
• Authors: Christina R. Mura...; Constance Zhou; Meichen Liao; Marty A. Fernandez; Walter M. Taylor; Valentina N. Lago...; Richard V. Pearse; Heather C. Rice; Joseph M. Negri; Amy He; Priya Srikanth; Dana G. Callahan; Taehwan Shin; Monica Zhou; David A. Bennett; Scott Noggle; J. Christopher Love; Dennis J. Selkoe; Tracy L. Young-Pe...
• Keywords: Cell type

Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor sensory deficits during its early middle course. A major unresolved question is basis for this selective neuronal vulnerability. Aβ, which plays a central role AD pathogenesis, generated throughout brain, yet some regions outside limbic cerebral cortices are relatively spared from Aβ plaque deposition synapse loss. Here, we examine neurons derived iPSCs patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation rostral fates brain (vulnerable) caudal (relatively spared) AD. We find that both generation responsiveness TAU affected by cell type, with being more sensitive than neurons. Thus, cell-autonomous factors may part dictate pattern regional vulnerability human