Imaging of tau deposits in adults with Niemann-Pick type C disease: a case-control study
Niemann-Pick type C (NPC) is a cholesterol storage disease characterized by disruption in the endosomal–lysosomal transport system that leads to the accumulation of cholesterol and glycolipids in lysosomes. Developmental cognitive delay and progressive motor and cognitive impairment are characteristic of the disease. Tau accumulation has been reported in some NPC patients. We investigated the presence of tau and Aβ-amyloid deposits in a group of NPC patients and for comparison in age-matched healthy controls (HC).
Eight NPC patients and seven HC were included in the study. Participants underwent tau imaging with 18F-AV1451 and amyloid imaging with 11C-PiB. Both 18F-AV1451 and 11C-PiB standardized uptake value ratios were generated using the cerebellar cortex as the reference region. Associations between imaging results, and clinical and neurocognitive parameters were assessed through nonparametric analyses.
All participants were Aβ-negative. Four NPC patients presented with high tau burden in the brain. A 21-year-old female patient and a 40-year-old male patient showed high neocortical tau burden in a pattern different from that observed in patients with Alzheimer’s disease, while the same 40-year-old male patient, a 40-year-old female patient and a 50-year-old female patient showed high regional tau burden in the mesial temporal cortex. Spearman’s correlation analysis showed an association between tau burden in the mesial temporal lobe and age (p = 0.022), and age at symptom onset (p = 0.009), and between frontotemporal tau and duration of symptoms (p = 0.027). There were no correlations between global and regional tau and cognitive parameters.
Four of eight NPC patients showed tau deposition in the brain. The results of our exploratory study suggest that while tau deposits do not affect cognitive performance, tau deposits are associated with measures of disease onset and progression. Further studies in a larger cohort of NPC patients are needed to confirm these initial findings.
KeywordsNiemann-Pick type C disease Tau pathology Tau imaging Amyloid imaging Cognitive impairment Disease severity
We thank Avid Radiopharmaceuticals for providing AV1451 precursor and standard, especially Drs. Michael Pontecorvo and Michael Devous, for kindly providing 18F-AV1451 images of three young adults used for age-matched comparison with young NPC patients. We also thank Dr. Graeme O’Keefe, Dr. Gordon Chan, Dr. Kenneth Young, Dr. Sylvia Gong, Mrs. Denise El-Sheikh; and the Brain Research Institute for their assistance with this study.
V.L.V. and M.W. conceived and designed the research. V.L.V., M.W., D.V., V.D., S.B., C.L.M. and C.C.R. performed the research and participated in the drafting of the work and revising it critically for important intellectual content. V.L.V. and M.W. wrote the paper with input from all authors.
This work was supported in part by the Austin Hospital Medical Research Foundation. The funding source was not involved in the study design, in the collection, analysis and interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.
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Conflicts of interest
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