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 - de Jong, Frank Jan
AU - van de Berg, Wilma D.J.
AU - Bonifati, Vincenzo
AU - Netherlands Brain Bank
PY - 2020/1/1
Y1 - 2020/1/1
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.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.
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.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.
KW - Genetic predisposition to disease
KW - genotype
KW - LRP10
KW - neuropathology
KW - phenotype
UR - http://www.scopus.com/inward/record.url?scp=85089358717&partnerID=8YFLogxK
U2 - 10.3233/JAD-200318
DO - 10.3233/JAD-200318
M3 - Article
C2 - 32597809
AN - SCOPUS:85089358717
VL - 76
SP - 1161
EP - 1170
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -