Background: Rare variants in the low-density lipoprotein receptor related protein 10 gene (LRP10) have recently been implicated in the etiology of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Objective: We searched for LRP10 variants in a new series of brain donors with dementia and Lewy pathology (LP) at autopsy, or dementia and parkinsonism without LP but with various other neurodegenerative pathologies. Methods: Sanger sequencing of LRP10 was performed in 233 donors collected by the Netherlands Brain Bank. Results: Rare, possibly pathogenic heterozygous LRP10 variants were present in three patients: p.Gly453Ser in a patient with mixed Alzheimer’s disease (AD)/Lewy body disease (LBD), p.Arg151Cys in a DLB patient, and p.Gly326Asp in an AD patient without LP. All three patients had a positive family history for dementia or PD. Conclusion: Rare LRP10 variants are present in some patients with dementia and different brain pathologies including DLB, mixed AD/LBD, and AD. These findings suggest a role for LRP10 across a broad neurodegenerative spectrum.

Additional Metadata
Keywords Genetic predisposition to disease, genotype, LRP10, neuropathology, phenotype
Persistent URL dx.doi.org/10.3233/jad-200318, hdl.handle.net/1765/130636
Journal Journal of Alzheimer's Disease
Citation
Vergouw, L.J.M., Geut, H., Breedveld, G.J, Kuipers, D.J.S., Quadri, M, Bank, N.B., … Bonifati, V. (2020). Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia. Journal of Alzheimer's Disease, 76(3), 1161–1170. doi:10.3233/jad-200318