Familial Alzheimers disease associated with heterozygous NPC1 mutation

We describe a novel NPC1 heterozygous mutation harboured by different members of a family with autosomal dominant late-onset amnesic AD without NPC-associated features. A missense mutation in homozygous state in the same aminoacidic position has been previously reported in a patient with NPC with severe phenotype. The alteration of serum oxysterols in our family corroborates the pathogenic role of our NPC1 mutation. Our work, illustrating clinical and biochemical disease hallmarks associated with NPC1 heterozygosity in patients affected by AD, provides relevant insights into the pathogenetic mechanisms underlying this possible novel association.

Source: Journal of Medical Genetics - March 21, 2024 Category: Genetics & Stem Cells Authors: Lopergolo, D., Bianchi, S., Gallus, G. N., Locci, S., Pucci, B., Leoni, V., Gasparini, D., Tardelli, E., Chincarini, A., Sestini, S., Santorelli, F. M., Zetterberg, H., De Stefano, N., Mignarri, A. Tags: Neurogenetics Source Type: research