Impact of <scp><i>APOE</i></scp> Genotype on Cognition in Idiopathic and Genetic Forms of Parkinson's Disease

Koros, Christos; Brockmann, Kathrin; Simitsi, Athina‐Maria; Bougea, Anastasia; Liu, Hui; Hauser, Ann‐Kathrin; Schulte, Claudia; Lerche, Stefanie; Pachi, Ioanna; Papagiannakis, Nikolaos; Antonelou, Roubina; Zahou, Athina; Wurster, Isabel; Efthymiopoulou, Efthymia; Beratis, Ion; Maniati, Matina; Μωραιτου, Μαρινα; Michelakakis, Helen; Paraskevas, George P.; Papageorgiou, Sokratis G.; Potagas, Constantin; Papadimitriou, Dimitra; Bozi, Maria; Stamelou, María; Gasser, Thomas; Stefanis, Leonidas

doi:10.1002/mds.29399

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…GBA1 is a major lysosomal risk locus for both PD 28 and DLB 29 . Variants in GBA1 have been linked to more rapid cognitive decline and increased risk of dementia in PD 5‐7,30,31 . Additionally, our results suggest lysosomal variants beyond GBA1 contribute to cognitive decline, as the association between the lysosomal PD‐PRS excluding GBA1 and time to dementia remained significant in PPMI and PDBP subjects with a low CSF and genetic vulnerability to AD co‐pathology, respectively.…”

Section: Discussionmentioning

confidence: 55%

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk

Tunold,

Tan,

Toft

et al. 2023

Movement Disorders

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BackgroundGenetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem.ObjectivesTo assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk.MethodsUsing Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk.ResultsThe lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively).ConclusionOur study supports complex interplay between genetics and neuropathology in Parkinson's disease‐related cognitive impairment, emphasizing the role of lysosomal polygenic burden. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 55%

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk

Tunold,

Tan,

Toft

et al. 2023

Movement Disorders

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“…Researches showed that decreased CSF Aβ42 can be detected in the preclinical stage of AD patients [ 30 ]. Previous studies also showed that PD patients who carry APOEε4 have lower CSF Aβ42 level and worse cognitive function than non-carriers [ 31 , 32 ]. Our study further demonstrates the impact of APOEε4 on CSF Aβ42 in PD patients even in the absence of obvious cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson’s disease

Zhu,

Chen,

Xiao

et al. 2024

Eur J Med Res

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Background Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. Methods A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson’s Progression Marker Initiative (PPMI). Results No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aβ42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. Conclusions APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aβ42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

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BIN3rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson’s disease

Chen

et al. 2023

Preprint

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Background Excessive daytime sleepiness (EDS) is one of the most common non-motor symptoms in Parkinson's disease (PD). Previous studies showed that PD patients with EDS exhibited more severe motor and non-motor symptoms. Our recent studies revealed that BIN3 rs2280104 was negatively associated with scores of Epworth Sleepiness Scale (ESS) in PD patients. The objective of this study is to examine whether BIN3 rs2280104 shapes brain networks of PD patients and whether network metrics associated with BIN3 rs2280104 mediate the effects of BIN3 rs2280104 on EDS. Methods PD patients (n = 144) receiving functional magnetic resonance imaging in Parkinson's Progression Markers Initiative (PPMI) database were investigated. The clinical manifestations and graphical metrics of structural and functional network were compared among different genotype groups of BIN3 rs2280104. The mediation analysis was used to explore the causal associations between network metrics modified by BIN3 rs2280104 and EDS of PD patients. Results ESS scores were associated with more severe motor and non-motor symptoms. BIN3 rs2280104 T allele was negatively associated with ESS scores in PD patients. Additionally, BIN3 rs2280104 significantly shaped structural and functional network metrics of PD patients. The nodal Cp of left superior temporal pole in functional network and the degree centrality of left calcarine in structural network were negatively associated with ESS scores, however, only the degree centrality of left calcarine in structural network mediated the effects of BIN3 rs2280104 on EDS of PD patients. Conclusions To summarize, BIN3 rs2280104 is significantly associated with EDS and network topology of PD patients. Additionally, the degree centrality of left calcarine in structural network mediated the effects of BIN3 rs2280104 on EDS. Future studies were required to identify the molecular mechanisms underlying the effects of BIN3 rs2280104 on EDS and brain network metrics of PD patients.

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Impact of APOE Genotype on Cognition in Idiopathic and Genetic Forms of Parkinson's Disease

Cited by 4 publications

References 7 publications

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson’s disease

BIN3rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson’s disease

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