ArticleiScience2026
Neurodegeneration in the olfactory system in Niemann Pick type C1 disease.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Niemann-Pick type C1 (NPC1) disease is a rare neurodegenerative disorder linked to defective cholesterol biosynthesis. Because olfactory dysfunction frequently precedes clinical manifestations in neurodegenerative conditions, we investigated whether the olfactory system might provide early insights into disease processes in NPC1. Using a knock-in mouse model carrying the human I1061T mutation, we investigated the olfactory epithelium in wild-type, heterozygous, and mutant mice to analyze neurodegeneration at 36 and 60 days after birth. Mutant mice showed reduced density of mature olfactory sensory neurons, increased apoptosis, and infiltration of macrophage/microglia. These structural alterations were accompanied by reduced odor-evoked responses and impaired odor-guided behavior. Finally, we assessed olfaction in a family with a child carrying biallelic NPC1 mutations and two heterozygous carrier parents, finding hyposmia of different severity in all three individuals. Our work extensively characterized the OE structurally and functionally, proposing it as a sentinel to monitor disease progression.
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