APOE, MAPT, and COMT and Parkinson’s Disease Susceptibility and Cognitive Symptom Progression
| Autor: | Jeff M. Bronstein, Michelle M. Creek, Yvette Bordelon, Kimberly C. Paul, Rebecca Rausch, Janet S. Sinsheimer, Beate Ritz |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oncology Apolipoprotein E medicine.medical_specialty Parkinson's disease Genotype tau Proteins Context (language use) Catechol O-Methyltransferase Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience Apolipoproteins E Cognition 0302 clinical medicine Internal medicine medicine Humans Dementia Genetic Predisposition to Disease Cognitive decline Psychiatry Aged Catechol-O-methyl transferase medicine.diagnostic_test Neuropsychology Parkinson Disease Neuropsychological test Middle Aged medicine.disease 030104 developmental biology Disease Progression Female Neurology (clinical) Psychology 030217 neurology & neurosurgery |
| Zdroj: | Journal of Parkinson's Disease. 6:349-359 |
| ISSN: | 1877-718X 1877-7171 |
| DOI: | 10.3233/jpd-150762 |
| Popis: | Background: Cognitive decline is well recognized in Parkinson’s disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. Objective: Here, we investigate whether APOE, COMT ,o rMAPT influence the rate of cognitive decline in PD patients. Methods: We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. Results: The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOE 4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. Conclusion: This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer’s disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE 4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD. |
| Databáze: | OpenAIRE |
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