Apolipoprotein E genotype and neurological disease onset in Niemann-Pick disease, type C1

Rao Fu, Nicole M. Yanjanin, Matthew J. Elrick, Christopher Ware, Andrew P. Lieberman, Forbes D. Porter

Research output: Contribution to journalArticlepeer-review


Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder that results in progressive neurological impairment. The NPC1 phenotype is extremely variable and at the individual level is likely influenced by other genetic traits. In addition to residual function of NPC1 protein, we hypothesize that modifier genes, as frequently observed with other autosomal recessive diseases, influence the NPC phenotype. The NPC1 phenotype includes progressive dementia, and the NPC pathology has some overlap with the pathology of Alzheimer disease (AD). Thus, we examined apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) polymorphisms in a cohort of 15 NPC1 patients with well characterized longitudinal disease progression. Although we did not find any correlations between disease severity and tau polymorphisms, we found significant associations between ApoE polymorphisms and phenotypic severity. Specifically, ApoE4 and ApoE2 alleles were associated, respectively, with increased and decreased disease severity in this cohort of NPC1 patients. These data support the hypothesis that ApoE may play a role in modulating NPC1 neuropathology.

Original languageEnglish (US)
Pages (from-to)2775-2780
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number11
StatePublished - Nov 2012
Externally publishedYes


  • Apolipoprotein E
  • Lysosomal storage disease
  • Neurodegenerative disease
  • Tau

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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