Potential contribution of the Alzheimer׳s disease risk locus BIN1 to episodic memory performance in cognitively normal Type 2 diabetes elderly

Greenbaum, Lior; Ravona‐Springer, Ramit; Lubitz, Irit; Schmeidler, James; Cooper, Itzik; Sano, Mary; Silverman, Jeremy M.; Heymann, Anthony; Beeri, Michal Schnaider

doi:10.1016/j.euroneuro.2015.11.004

Cited by 15 publications

(8 citation statements)

References 45 publications

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“…The hippocampus is a bilateral brain structure located in the temporal lobe on which learning and memory are critically dependant [ 53 ]. Episodic memory impairment is a hallmark of neurodegenerative diseases, such as Alzheimer’s disease, which are neurobiologically linked to the hippocampus [ 54 ]. Liu and colleagues [ 48 ] reported that Pb exposure induced significant microgliosis and astrogliosis in hippocampus of young mice.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats

Suleman

Engwa

Shauli

et al. 2022

BMC Complement Med Ther

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Background Though Lippia javanica (Burm.f.) Spreng antioxidant activity has been demonstrated, its effect in protecting the brain from lead (Pb)-induced oxidative damage is unknown. This study investigated the effect of L. javanica against Pb-induced oxidative stress, inflammation, apoptosis and acetylcholinesterase activity in rat’s brain. Methods L. javanica herbal tea infusion was prepared, its phytochemical constituent was revealed by liquid chromatography-Mass spectrometer (LC-MS) and was administered simultaneously with Pb. Four groups of male Wistar rats (n = 5/group) were used: control received distilled water; Pb-acetate group received 50 mg Pb/ Kg bodyweight (bw), treatment group received 50 mg Pb/ Kg Pb-acetate + 5 ml/kg bw L. javanica and L. javanica group received 5 ml/Kg bw of L. javanica tea infusion only. After 6 weeks of treatment, oxidative status, acetylcholinesterase activity, inflammation and apoptosis was assessed in brain tissue which was also histologically examined. Results Mean brain and heart weight was reduced (p < 0.05) while liver and spleen weights were increased (p < 0.05) in Pb exposed animals but were prevented by L. juvanica treatment. Treatment with L. javanica increased (p < 0.05) overall brain antioxidant status (glutathione and superoxide dismutase activities) and reduced lipid peroxidation (p < 0.05) compared to the Pb exposed animals. Pro-inflammatory cytokine tumour necrotic factor-alpha, pro-apoptosis Bax protein and anticholinesterase activity were reduced (p < 0.05) in Pb-L. javanica treated animals compared to the Pb exposed group. Histological examination confirmed neuroprotective effects of L. javanica as evidenced by reduced apoptosis/necrosis and inflammation-induced vacuolization and oedema in the hippocampus. The L. javanica treatment alone had no detrimental effects to the rats. LC-MS analysis revealed L. javanica to be rich in phenolics. Conclusions This study demonstrated that L. javanica, rich in phenolics was effective in reducing Pb-induced brain oxidative stress, inflammation, apoptosis, acetylcholinesterase activity and neuronal damage.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats

Suleman

Engwa

Shauli

et al. 2022

BMC Complement Med Ther

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Section: Discussionmentioning

confidence: 91%

“…rs6733839 carriage is associated with higher pTau181 levels in CSF ( Crotti et al, 2019 ). Homozygote individuals for rs6733839*T show worse episodic memory ( Greenbaum et al, 2016 ). This SNP is in LD with rs4663105, which occurs in the NONHSAT187478.1 lncRNA gene, possibly associated with neurodegenerative diseases (ncRPheno).…”

Section: Discussionmentioning

confidence: 99%

GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs

Kretzschmar

Alencar

Silva

et al. 2021

Front. Mol. Biosci.

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Several genome-wide association studies (GWAS) have been carried out with late-onset Alzheimer’s disease (LOAD), mainly in European and Asian populations. Different polymorphisms were associated, but several of them without a functional explanation. GWAS are fundamental for identifying loci associated with diseases, although they often do not point to causal polymorphisms. In this sense, functional investigations are a fundamental tool for discovering causality, although the failure of this validation does not necessarily indicate a non-causality. Furthermore, the allele frequency of associated genetic variants may vary widely between populations, requiring replication of these associations in other ethnicities. In this sense, our study sought to replicate in 150 AD patients and 114 elderly controls from the South Brazilian population 18 single-nucleotide polymorphisms (SNPs) associated with AD in European GWAS, with further functional investigation using bioinformatic tools for the associated SNPs. Of the 18 SNPs investigated, only four were associated in our population: rs769449 (APOE), rs10838725 (CELF1), rs6733839, and rs744373 (BIN1–CYP27C1). We identified 54 variants in linkage disequilibrium (LD) with the associated SNPs, most of which act as expression or splicing quantitative trait loci (eQTLs/sQTLs) in genes previously associated with AD or with a possible functional role in the disease, such as CELF1, MADD, MYBPC3, NR1H3, NUP160, SPI1, and TOMM40. Interestingly, eight of these variants are located within long non-coding RNA (lncRNA) genes that have not been previously investigated regarding AD. Some of these polymorphisms can result in changes in these lncRNAs’ secondary structures, leading to either loss or gain of microRNA (miRNA)-binding sites, deregulating downstream pathways. Our pioneering work not only replicated LOAD association with polymorphisms not yet associated in the Brazilian population but also identified six possible lncRNAs that may interfere in LOAD development. The results lead us to emphasize the importance of functional exploration of associations found in large-scale association studies in different populations to base personalized and inclusive medicine in the future.

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“…Meanwhile, a meta-analysis of 74,046 participants found that BIN1 rs6733839 SNP was related to AD [ 33 ]. Greenbaum et al observed an association between well-established AD susceptibility SNP rs6733839 and episodic memory, and it can an important genetic risk factor for MCI among elderly individuals [ 34 ]. Based on the above studies, we have reason to believe that rs6733839 and rs7561528 gene polymorphism occupy a vital position in the pathogenesis of MCI by affecting the expression of BIN1.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of mild cognitive impairment genetic susceptibility risks in a Chinese population

Zhang

et al. 2022

BMC Psychiatry

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Background Mild cognitive impairment (MCI) is a kind of non-functional cognitive decline between normal aging and dementia. With the increase of individual age, the quality of cognitive function has become a more and more important topic. The study of gene loci in patients with MCI is essential for the prevention of dementia. In this study, we evaluate the gene polymorphism in Chinese Han patients with MCI by propensity score matching (PSM) and comparing them to healthy control (HC) subjects. Methods Four hundred seventeen patients with mild cognitive impairment and 508 healthy people were included. The two groups were matched by applying one-to-one PSM, and the matching tolerance was set to 0.002. The matching covariates included gender,age,occupation,marital status,living mode. Then, a case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the control group. Results Three hundred eleven cases were successfully matched in each group, and there was no statistical difference on all the matching variables, gender, age, occupation, marital status, living mode between two groups after the match (P > 0.05). The allele frequency of bridging integrator 1(BIN1) rs7561528 showed minimal association with MCI in the Han Chinese population (P = 0.01). Compared with the healthy control (HC) group, A allele frequency of MCI group patients was significantly decreased. The genotype frequency of BIN1 rs6733839 showed minimal association with MCI in the recessive model (P = 0.03). The genotype frequency of rs7561528 showed minimal association with MCI in the codominant, dominant, overdominant, and log-additive model (P < 0.05). The genotype frequencies of StAR-related lipid transfer domain 6 (STARD6) rs10164112 showed nominal association with MCI in the codominant, dominant, and log-additive model (P < 0.05). Unfortunately, the significant differences did not survive Benjamini-Hochberg false discovery rate correction (adjusted P > 0.05). The patients with SPI1 rs1057233 may be the protective factor of MCI (OR = 0.733, 95%CI 0.625–0.859, P < 0.001), and patients with APOE rs10164112 may be a risk factor for MCI (OR = 1.323, 95%CI 1.023–1.711, P = 0.033). Conclusions The polymorphisms of rs7561528, rs6733839 loci in the BIN1 gene, and rs1057233 loci in the SPI1 gene may be associated with the MCI in Chinese Han population. APOE gene was the risk factor of MCI, but further verification in a large sample population is still needed.

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Potential contribution of the Alzheimer׳s disease risk locus BIN1 to episodic memory performance in cognitively normal Type 2 diabetes elderly

Cited by 15 publications

References 45 publications

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats

GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs

Evaluation of mild cognitive impairment genetic susceptibility risks in a Chinese population

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