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Abstract
Objective: To evaluate whether genetic variants in β-amyloid (Aβ) clearance proteins are associated with CSF levels of Aβ1-42 on a biological level and the onset of dementia on a clinical level in Parkinson disease (PD).
Methods: We analyzed genetic variants known to be involved in Aβ clearance in a PD group comprising 456 patients, 103 of them with dementia. Single nucleotide polymorphisms in the genes APOE, cystatin C (CST), and membrane metalloendopeptidase (MME) were evaluated in relation to demographic variables, clinical phenotypes, and CSF Aβ1-42 levels using a cross-sectional approach.
Results: Risk variants in the genes APOE and CST were associated with lower CSF Aβ1-42 levels. Clinically, patients with 2 risk alleles in CST tended to show a shorter interval from age at onset of PD to age at onset of dementia.
Conclusions: This study suggests that genetic variants associated with Aβ clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.
GLOSSARY
- AD=
- Alzheimer disease;
- CST3=
- cystatin C;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- MME=
- membrane metalloendopeptidase;
- MMSE=
- Mini-Mental State Examination;
- PD=
- Parkinson disease;
- PDD=
- Parkinson disease with dementia;
- PDND=
- Parkinson disease without dementia;
- SNP=
- single nucleotide polymorphism
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received November 23, 2016.
- Accepted in final form August 30, 2017.
- © 2017 American Academy of Neurology
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