Presenilin 1 Mutation (A431V) Causing Features of Dementia with Lewy Bodies in a Chinese Family of Alzheimer’s Disease

Qiao, Yanan; Peng, Dantao; Jin, Miao; Xue, Shifeng

doi:10.4172/2161-0460.1000307

Cited by 2 publications

(2 citation statements)

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“…Recently, it was reported that a de novo PSEN1 mutation is responsible for an early-onset parkinsonism with cognitive impairment (Carecchio et al, 2017 ). In addition to the clinical overlap between dementia and parkinsonism in carriers of PSEN1 mutations, there is extensive Lewy body pathology in early-onset AD carriers of the PSEN1 p.S170F (Snider et al, 2005 ) and PSEN1 p.A431V mutations (Qiao et al, 2017 ) suggesting an interaction between PSEN1 dysfunction and α-synuclein aggregation.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease

et al. 2018

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Background: The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients.Methods: We analyzed the coding regions of the amyloid-beta precursor protein (APP), Presenilin 1 and 2 (PSEN1, PSEN2), and Granulin (GRN) genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES) data by single variant and gene base (SKAT-O and burden tests) analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status.Results: Known AD pathogenic mutations in the PSEN1 (p.A79V) and PSEN2 (p.V148I) genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2, and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients (p = 2.0 × 10−4), independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site.Conclusions: Pathogenic mutations in the Alzheimer disease-causing genes (PSEN1 and PSEN2) are found in sporadic PD patients. PD patients with cognitive decline carry rare variants in dementia-causing genes. Variants in genes causing Mendelian neurodegenerative diseases exhibit pleiotropic effects.

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Section: Discussionmentioning

confidence: 99%

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease

et al. 2018

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“…1 A rarely reported PSEN1-associated phenotype is dementia with Lewy bodies (DLB). [1][2][3][4][5] DLB is seen as a distinct clinical entity, presenting certain characteristic observations, albeit that there is considerable clinical overlap with AD, as Vergouw et al 6 discuss and illustrate in a postmortem study of "false-positive" or "mimic" DLB. We here describe a further case of PSEN1-associated mimic DLB.…”

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confidence: 99%