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.

Genetic predisposition to disease, genotype, LRP10, neuropathology, phenotype,
Journal of Alzheimer's Disease
Department of Clinical Genetics

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