Modeling Brain Pathology of Niemann-Pick Disease Type C Using Patient-Derived Neurons

Lena F. Burbulla, Jessica M. Mc Donald, Clarissa Valdez, Fanding Gao, Eileen H. Bigio, Dimitri Krainc*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Niemann-Pick disease type C (NPC) is a rare autosomal-recessive lysosomal storage disease that is also associated with progressive neurodegeneration. NPC shares many pathological features with Alzheimer's disease, including neurofibrillary tangles, axonal spheroids, β-amyloid deposition, and dystrophic neurites. Here, we examined if these pathological features could be detected in induced pluripotent stem cell (iPSC)-derived neurons from NPC patients. Methods: Brain tissues from 8 NPC patients and 5 controls were analyzed for histopathological and biochemical markers of pathology. To model disease in culture, iPSCs from NPC patients and controls were differentiated into cortical neurons. Results: We found hyperphosphorylated tau, altered processing of amyloid precursor protein, and increased Aβ42 in NPC postmortem brains and in iPSC-derived cortical neurons from NPC patients. Conclusion: Our findings demonstrated that the main pathogenic phenotypes typically found in NPC brains were also observed in patient-derived neurons, providing a useful model for further mechanistic and therapeutic studies of NPC.

Original languageEnglish (US)
Pages (from-to)1022-1027
Number of pages6
JournalMovement Disorders
Issue number4
StatePublished - Apr 2021


  • Niemann-Pick disease; iPSC; disease modeling; brain pathology

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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