Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease

Zhou, Lin; Li, Haiyan; Wang, Jihui; Deng, Zhezhi; Shan, Yingchun; Tan, Sha; Shi, Yonghong; Zhang, Mingxing; Liu, San-Xin; Zhang, Bing-Jun; Hong, Ming‐Fan; Liu, Zhengqi; Huang, Xuming

doi:10.1097/md.0000000000012470

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…Concurrent to these and to our study, Garcia et al 54 Regarding the genotypic frequencies of the APOE gene, Zhou et al 40 and Demarchi et al 56 presented results very similar to those found in this meta-analysis. When evaluated together, they demonstrated that the Ԑ4 allele plays a role as a risk factor, while the Ԑ2 allele has a protective factor weight, agreeing with our results on its association with the genetic protection condition.…”

Section: Discussionsupporting

confidence: 91%

Association between alzheimer’s disease and apoe gene genotypic polymorphisms: systematic review and meta-analysis / Associação entre doença de alzheimer e polimorfismos genotipicos do gene apoe: revisão sistemática e metanálise

Pereira¹,

Gonçalves²,

Silva³

et al. 2021

BJDV

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Introduction-Alzheimer's disease (AD) is classified as neurodegenerative, progressive and irreversible and is clinically characterized by a progressive decline in neurological functions. Objective-To evaluate the association among the genotypic variations of the APOE gene with Alzheimer's Disease. Methods-This is a systematic review and metaanalysis, and, according to the inclusion criteria, 59 articles were selected from the PubMed, Latin American and Caribbean Literature in Health Sciences (LILACS) and Scientific databases Electronic Library Online (SciELO) and of this total, 22 contributed data for systematic review and meta-analysis. Statistical tests were performed with the aid of the STATA® 16.0 software, considering the significance limit equal to 5% (pvalue = 0.05). Thus, the DerSimonian-Laird and Mantel Haenszel tests were applied according to heterogeneity, for the evaluation of Odds Ratios (OR). Results-The results showed an association of predisposition to the development of AD, considering the genotypes Ԑ3Ԑ4 and Ԑ4Ԑ4, respectively OR = 2.63 (95% CI = 2.18-318) and OR = 5.37 (95% CI = 3.57-8.08), on the other hand, the genotypes Ԑ2Ԑ3 and Ԑ3Ԑ3, showed

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Section: Discussionsupporting

confidence: 91%

Association between alzheimer’s disease and apoe gene genotypic polymorphisms: systematic review and meta-analysis / Associação entre doença de alzheimer e polimorfismos genotipicos do gene apoe: revisão sistemática e metanálise

Pereira¹,

Gonçalves²,

Silva³

et al. 2021

BJDV

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“…CD36 single nucleotide polymorphisms (SNP) have been linked to AD, some increasing the risk of AD [ 28 , 94 ] and others delaying disease onset [ 94 , 95 ]. In silico studies suggest that the protective SNP may suppress CD36-induced inflammation upon Aβ binding [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress

Uekawa,

Hattori,

Ahn

et al. 2023

Mol Neurodegeneration

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Background Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer’s disease but also observed in the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated in CAA but the cellular source of reactive oxygen species (ROS) and related signaling mechanisms remain unclear. We tested the hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal and leptomeningeal blood vessels, are the source of radicals through the Aβ-binding innate immunity receptor CD36, leading to neurovascular dysfunction, CAA, and cognitive impairment. Methods Tg2576 mice and WT littermates were transplanted with CD36−/− or CD36+/+ bone marrow at 12-month of age and tested at 15 months. This approach enables the repopulation of perivascular and leptomeningeal compartments with CD36−/− BAM. Neurovascular function was tested in anesthetized mice equipped with a cranial window in which cerebral blood flow was monitored by laser-Doppler flowmetry. Amyloid pathology and cognitive function were also examined. Results The increase in blood flow evoked by whisker stimulation (functional hyperemia) or by endothelial and smooth muscle vasoactivity was markedly attenuated in WT → Tg2576 chimeras but was fully restored in CD36−/− → Tg2576 chimeras, in which BAM ROS production was suppressed. CAA-associated Aβ1-40, but not Aβ1-42, was reduced in CD36−/− → Tg2576 chimeras. Similarly, CAA, but not parenchymal plaques, was reduced in CD36−/− → Tg2576 chimeras. These beneficial vascular effects were associated with cognitive improvement. Finally, CD36−/− mice were able to more efficiently clear exogenous Aβ1-40 injected into the neocortex or the striatum. Conclusions CD36 deletion in BAM suppresses ROS production and rescues the neurovascular dysfunction and damage induced by Aβ. CD36 deletion in BAM also reduced brain Aβ1-40 and ameliorated CAA without affecting parenchyma plaques. Lack of CD36 enhanced the vascular clearance of exogenous Aβ. Restoration of neurovascular function and attenuation of CAA resulted in a near complete rescue of cognitive function. Collectively, these data implicate brain BAM in the pathogenesis of CAA and raise the possibility that targeting BAM CD36 is beneficial in CAA and other conditions associated with vascular Aβ deposition and damage. Graphical Abstract

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“…Presence of one or two ApoE4 alleles implies a greater risk of LOAD, lower age of onset, more severe course of disease and poorer treatment response 13 , 14 . In addition to ApoE4, several other polymorphisms in various candidate genes have recently been identified as associated with LOAD 15 – 21 . The present study focuses on the polymorphisms of the candidate gene CD36 (“cluster of differentiation” 36).…”

Section: Introductionmentioning

confidence: 99%

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

Šerý

Zeman

Sheardová

et al. 2022

Sci Rep

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The risk of Alzheimer’s disease (AD) has a strong genetic component, also in the case of late-onset AD (LOAD). Attempts to sequence whole genome in large populations of subjects have identified only a few mutations common to most of the patients with AD. Targeting smaller well-characterized groups of subjects where specific genetic variations in selected genes could be related to precisely defined psychological traits typical of dementia is needed to better understand the heritability of AD. More than one thousand participants, categorized according to cognitive deficits, were assessed using 14 psychometric tests evaluating performance in five cognitive domains (attention/working memory, memory, language, executive functions, visuospatial functions). CD36 was selected as a gene previously shown to be implicated in the etiology of AD. A total of 174 polymorphisms were tested for associations with cognition-related traits and other AD-relevant data using the next generation sequencing. Several associations between single nucleotide polymorphisms (SNP’s) and the cognitive deficits have been found (rs12667404 with language performance, rs3211827 and rs41272372 with executive functions, rs137984792 with visuospatial performance). The most prominent association was found between a group of genotypes in six genetically linked and the age at which the AD patients presented with, or developed, a full-blown dementia. The identified alleles appear to be associated with a delay in the onset of LOAD. In silico studies suggested that the SNP’s alter the expression of CD36 thus potentially affecting CD36-related neuroinflammation and other molecular and cellular mechanisms known to be involved in the neuronal loss leading to AD. The main outcome of the study is an identification of a set of six new mutations apparently conferring a distinct protection against AD and delaying the onset by about 8 years. Additional mutations in CD36 associated with certain traits characteristic of the cognitive decline in AD have also been found.

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Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease

Cited by 9 publications

References 25 publications

Association between alzheimer’s disease and apoe gene genotypic polymorphisms: systematic review and meta-analysis / Associação entre doença de alzheimer e polimorfismos genotipicos do gene apoe: revisão sistemática e metanálise

Association between alzheimer’s disease and apoe gene genotypic polymorphisms: systematic review and meta-analysis / Associação entre doença de alzheimer e polimorfismos genotipicos do gene apoe: revisão sistemática e metanálise

Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

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