Academic Journal
A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer's disease.
| Τίτλος: | A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer's disease. |
|---|---|
| Συγγραφείς: | Fan, Wei, Wang, Ziqi, Wan, Shu, Liu, Man, Han, Yuanyuan, Liu, Xiaowei, Xu, Lisi, Wang, Xiaoyan, Zhang, Dingyi, Cai, Qingyan |
| Πηγή: | Frontiers in Psychiatry; 2026, p1-10, 10p |
| Θεματικοί όροι: | Apolipoprotein E, Alzheimer's disease, Neurobehavioral disorders, Genotypes, White matter (Nerve tissue), Mediation (Statistics), Cognition disorders, Psychiatric diagnosis |
| Περίληψη: | Objective: This study investigates the independent and interactive effects of apolipoprotein E (APOE) genotypes and white matter hyperintensities (WMH) on distinct neuropsychiatric symptom (NPS) phenotypes in patients with Alzheimer's disease (AD). Methods: We enrolled 325 AD patients consecutively diagnosed at a specialized memory clinic between May 2024 and May 2025. All participants underwent comprehensive clinical assessments—including the Chinese Mini-Mental State Examination (CMMSE), Activities of Daily Living (ADL) scale, and the Neuropsychiatric Inventory (NPI)—as well as 3T brain MRI for WMH quantification and APOE genotyping. First, we compared NPS profiles and cognitive/functional scores across APOE genotype groups (ϵ2/ϵ2–ϵ2/ϵ3, ϵ3/ϵ3, ϵ3/ϵ4, ϵ4/ϵ4) using analysis of variance (ANOVA) or Kruskal–Wallis tests, as appropriate. Second, we applied mediation analysis (PROCESS macro Model 4, 5,000 bootstrap samples) to examine whether WMH burden mediates the association between APOE genotype (X) and outcomes including CMMSE total score and domain-specific NPS subscores (delusions, agitation, irritability, euphoria). Results: Significant differences emerged across APOE genotypes in both cognition (CMMSE, p < 0.05) and functional status (ADL, p < 0.05). At the symptom level, carriers of at least one ϵ4 allele exhibited higher agitation scores than non-carriers (p < 0.05); notably, the ϵ4/ϵ4 homozygotes showed significantly greater severity in delusions, agitation, irritability, and euphoria compared with all other genotype groups (all p < 0.05). Mediation analyses revealed no statistically significant indirect effect of APOE genotype on any outcome via WMH, indicating that WMH does not mediate these associations. Instead, APOE genotype exerted robust direct effects on both cognitive performance and specific NPS domains. Conclusion: APOE genotype—particularly the ϵ4/ϵ4 homozygous status—is associated with more pronounced cognitive decline and a distinct, severe NPS profile in AD, especially involving delusions, agitation, Euphoria, and irritability. These associations are independent of WMH burden, suggesting that APOE exerts direct neurobiological effects on neuropsychiatric manifestations. Thus, APOE genotyping holds dual clinical value: not only as a well-established biomarker for AD risk and diagnosis but also as a potential prognostic indicator for behavioral and psychological symptoms—offering actionable insights beyond conventional neuroimaging markers. [ABSTRACT FROM AUTHOR] |
| Copyright of Frontiers in Psychiatry is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Βάση Δεδομένων: | Complementary Index |
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| Header | DbId: edb DbLabel: Complementary Index An: 192770707 RelevancyScore: 1041 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 1041.07470703125 |
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| Items | – Name: Title Label: Title Group: Ti Data: A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer's disease. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Fan%2C+Wei%22">Fan, Wei</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Ziqi%22">Wang, Ziqi</searchLink><br /><searchLink fieldCode="AR" term="%22Wan%2C+Shu%22">Wan, Shu</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Man%22">Liu, Man</searchLink><br /><searchLink fieldCode="AR" term="%22Han%2C+Yuanyuan%22">Han, Yuanyuan</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Xiaowei%22">Liu, Xiaowei</searchLink><br /><searchLink fieldCode="AR" term="%22Xu%2C+Lisi%22">Xu, Lisi</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Xiaoyan%22">Wang, Xiaoyan</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Dingyi%22">Zhang, Dingyi</searchLink><br /><searchLink fieldCode="AR" term="%22Cai%2C+Qingyan%22">Cai, Qingyan</searchLink> – Name: TitleSource Label: Source Group: Src Data: Frontiers in Psychiatry; 2026, p1-10, 10p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Apolipoprotein+E%22">Apolipoprotein E</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Neurobehavioral+disorders%22">Neurobehavioral disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Genotypes%22">Genotypes</searchLink><br /><searchLink fieldCode="DE" term="%22White+matter+%28Nerve+tissue%29%22">White matter (Nerve tissue)</searchLink><br /><searchLink fieldCode="DE" term="%22Mediation+%28Statistics%29%22">Mediation (Statistics)</searchLink><br /><searchLink fieldCode="DE" term="%22Cognition+disorders%22">Cognition disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Psychiatric+diagnosis%22">Psychiatric diagnosis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Objective: This study investigates the independent and interactive effects of apolipoprotein E (APOE) genotypes and white matter hyperintensities (WMH) on distinct neuropsychiatric symptom (NPS) phenotypes in patients with Alzheimer's disease (AD). Methods: We enrolled 325 AD patients consecutively diagnosed at a specialized memory clinic between May 2024 and May 2025. All participants underwent comprehensive clinical assessments—including the Chinese Mini-Mental State Examination (CMMSE), Activities of Daily Living (ADL) scale, and the Neuropsychiatric Inventory (NPI)—as well as 3T brain MRI for WMH quantification and APOE genotyping. First, we compared NPS profiles and cognitive/functional scores across APOE genotype groups (ϵ2/ϵ2–ϵ2/ϵ3, ϵ3/ϵ3, ϵ3/ϵ4, ϵ4/ϵ4) using analysis of variance (ANOVA) or Kruskal–Wallis tests, as appropriate. Second, we applied mediation analysis (PROCESS macro Model 4, 5,000 bootstrap samples) to examine whether WMH burden mediates the association between APOE genotype (X) and outcomes including CMMSE total score and domain-specific NPS subscores (delusions, agitation, irritability, euphoria). Results: Significant differences emerged across APOE genotypes in both cognition (CMMSE, p < 0.05) and functional status (ADL, p < 0.05). At the symptom level, carriers of at least one ϵ4 allele exhibited higher agitation scores than non-carriers (p < 0.05); notably, the ϵ4/ϵ4 homozygotes showed significantly greater severity in delusions, agitation, irritability, and euphoria compared with all other genotype groups (all p < 0.05). Mediation analyses revealed no statistically significant indirect effect of APOE genotype on any outcome via WMH, indicating that WMH does not mediate these associations. Instead, APOE genotype exerted robust direct effects on both cognitive performance and specific NPS domains. Conclusion: APOE genotype—particularly the ϵ4/ϵ4 homozygous status—is associated with more pronounced cognitive decline and a distinct, severe NPS profile in AD, especially involving delusions, agitation, Euphoria, and irritability. These associations are independent of WMH burden, suggesting that APOE exerts direct neurobiological effects on neuropsychiatric manifestations. Thus, APOE genotyping holds dual clinical value: not only as a well-established biomarker for AD risk and diagnosis but also as a potential prognostic indicator for behavioral and psychological symptoms—offering actionable insights beyond conventional neuroimaging markers. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Frontiers in Psychiatry is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3389/fpsyt.2026.1795598 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 1 Subjects: – SubjectFull: Apolipoprotein E Type: general – SubjectFull: Alzheimer's disease Type: general – SubjectFull: Neurobehavioral disorders Type: general – SubjectFull: Genotypes Type: general – SubjectFull: White matter (Nerve tissue) Type: general – SubjectFull: Mediation (Statistics) Type: general – SubjectFull: Cognition disorders Type: general – SubjectFull: Psychiatric diagnosis Type: general Titles: – TitleFull: A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer's disease. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Fan, Wei – PersonEntity: Name: NameFull: Wang, Ziqi – PersonEntity: Name: NameFull: Wan, Shu – PersonEntity: Name: NameFull: Liu, Man – PersonEntity: Name: NameFull: Han, Yuanyuan – PersonEntity: Name: NameFull: Liu, Xiaowei – PersonEntity: Name: NameFull: Xu, Lisi – PersonEntity: Name: NameFull: Wang, Xiaoyan – PersonEntity: Name: NameFull: Zhang, Dingyi – PersonEntity: Name: NameFull: Cai, Qingyan IsPartOfRelationships: – BibEntity: Dates: – D: 03 M: 04 Text: 2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 16640640 Titles: – TitleFull: Frontiers in Psychiatry Type: main |
| ResultId | 1 |