Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia

TY - JOUR

T1 - Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia

AU - Vergouw, Leonie J M

AU - Geut, Hanneke

AU - Breedveld, Guido

AU - Kuipers, Demy J S

AU - Quadri, Marialuisa

AU - Rozemuller, Annemieke J M

AU - van Swieten, John C

AU - van de Berg, Wilma D J

AU - Bonifati, Vincenzo

PY - 2020

Y1 - 2020

N2 - 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.Gly453Serin 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.

AB - 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.Gly453Serin 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.

U2 - 10.3233/JAD-200318

DO - 10.3233/JAD-200318

M3 - Article

C2 - 32597809

SN - 1387-2877

VL - 76

SP - 1161

EP - 1170

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

ER -