Редактирование: SORL1 (раздел)

==Publications==

{{medline-entry
|title=Single Nucleotide Polymorphisms in Alzheimer's Disease Risk Genes Are Associated with Intrinsic Connectivity in Middle Age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32986668
|abstract=It is critical to identify individuals at risk for Alzheimer's disease (AD) earlier in the disease time course, such as middle age and preferably well prior to the onset of clinical symptoms, when intervention efforts may be more successful. Genome-wide association and candidate gene studies have identified single nucleotide polymorphisms (SNPs) in [[APOE]], [[CLU]], [[CR1]], [[PICALM]], and [[SORL1]] that confer increased risk of AD. In the current study, we investigated the associations between SNPs in these genes and resting-state functional connectivity within the default mode network (DMN), frontoparietal network (FPN), and executive control network (ECN) in healthy, non-demented middle-aged adults (age 40 -60; N = 123; 74 females). Resting state networks of interest were identified through independent components analysis using a template-matching procedure and individual spatial maps and time courses were extracted using dual regression. Within the posterior DMN, functional connectivity was associated with [[CR1]] rs1408077 and [[CLU]] rs9331888 polymorphisms (p's < 0.05). FPN connectivity was associated with [[CR1]] rs1408077, [[CLU]] rs1136000, [[SORL1]] rs641120, and [[SORL1]] rs689021 (p's < 0.05). Functional connectivity within the ECN was associated with the [[CLU]] rs11136000 (p < 0.05). There were no [[APOE]]- or [[PICALM]]-related differences in any of the networks investigated (p's > 0.05). This is the first demonstration of the relationship between intrinsic network connectivity and AD risk alleles in [[CLU]], [[CR1]], and [[SORL1]] in healthy, middle-aged adults. These SNPs should be considered in future investigations aimed at identifying potential preclinical biomarkers for AD.

|keywords=* Aging
* Alzheimer’s disease
* middle aged
* neuroimaging
* single nucleotide 
polymorphism
|full-text-url=https://sci-hub.do/10.3233/JAD-200444
}}
{{medline-entry
|title=A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30706571
|abstract=While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). We analyzed 96 SNPs across five genes ([[APOE]]/[[TOMM40]], [[BDNF]], [[COMT]], [[SORL1]], and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. One SNP (rs157582), located in the [[TOMM40]] gene nearby [[APOE]], was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 ([[APOE]]: rs405509, rs439401; [[TOMM40]]: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of [[COMT]] rs737865 and [[BDNF]] rs1491850 (P ≤ 0.05). Our results in older women provide supporting evidence that the [[APOE]]/[[TOMM40]] genes confer dementia risk and extend these findings to [[COMT]], [[BDNF]], and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.
|mesh-terms=* Aged
* Alzheimer Disease
* Apolipoproteins E
* Brain-Derived Neurotrophic Factor
* Catechol O-Methyltransferase
* Cognitive Dysfunction
* Dementia
* Female
* Genetic Predisposition to Disease
* Humans
* Intracellular Signaling Peptides and Proteins
* LDL-Receptor Related Proteins
* Membrane Transport Proteins
* Middle Aged
* Polymorphism, Single Nucleotide
* Postmenopause
* Women's Health
|keywords=* AD
* Alzheimer's disease
* MCI
* aging
* hormone therapy
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608707
}}
{{medline-entry
|title=Genetic Risk for Age-Related Cognitive Impairment Does Not Predict Cognitive Performance in Middle Age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29865048
|abstract=Alzheimer's disease (AD) is characterized by memory loss and executive dysfunction, which correspond to structural changes to the medial temporal lobes (MTL) and prefrontal cortex (PFC), respectively. Given the overlap in cognitive deficits between healthy aging and the earliest stages of AD, early detection of AD remains a challenge. The goal of the present study was to study MTL- and PFC-dependent cognitive functioning in middle-aged individuals at genetic risk for AD or cognitive impairment who do not currently manifest any clinical symptoms. Participants (N = 150; aged 40-60 years) underwent genotyping of 47 single nucleotide polymorphisms (SNPs) in six genes previously associated with memory or executive functioning: [[APOE]], [[SORL1]], [[BDNF]], [[TOMM40]], KIBRA, and [[COMT]]. They completed two MTL-dependent tasks, the virtual Morris Water Task (vMWT) and transverse patterning discriminations task (TPDT), and the PFC-dependent reversal learning task. Although age was associated with poorer performance on the vMWT and TPDT within this middle-aged sample, there were no genotype-associated differences in cognitive performance. Although the vMWT and TPDT may be sensitive to age-related changes in cognition, carriers of [[APOE]], [[SORL1]], [[BDNF]], [[TOMM40]], KIBRA, and [[COMT]] risk alleles do not exhibit alteration in MTL- and PFC-dependent functioning in middle age compared to non-carriers.
|mesh-terms=* Adult
* Aging
* Analysis of Variance
* Apolipoproteins E
* Brain-Derived Neurotrophic Factor
* Catechol O-Methyltransferase
* Cognitive Dysfunction
* Executive Function
* Female
* Genotype
* Humans
* Independent Living
* Intracellular Signaling Peptides and Proteins
* LDL-Receptor Related Proteins
* Male
* Maze Learning
* Membrane Transport Proteins
* Middle Aged
* Phosphoproteins
* Polymorphism, Single Nucleotide
* Reaction Time
* User-Computer Interface
|keywords=* Aging
* Alzheimer’s disease
* apolipoproteins E
* brain-derived neurotrophic factor
* cognition
* hippocampus
* middle age
* prefrontal cortex
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263481
}}
{{medline-entry
|title=Genetic epistasis regulates amyloid deposition in resilient aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28322202
|abstract=The brain-derived neurotrophic factor ([[BDNF]]) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the [[SORL1]] gene determine [[BDNF]]'s ability to reduce amyloid β (Aβ) in vitro. We sought to test whether functional [[BDNF]] variation interacts with [[SORL1]] genotypes to influence expression and downstream AD-related processes in humans. We analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative. We found one [[SORL1]] RNA transcript strongly regulated by [[SORL1]]-[[BDNF]] interactions in elderly without pathological AD and showing stronger associations with diffuse than neuritic Aβ plaques. The same [[SORL1]]-[[BDNF]] interactions also significantly influenced Aβ load as measured with [ F]Florbetapir positron emission tomography. Our results bridge the gap between risk and resilience factors for AD, demonstrating interdependent roles of established [[SORL1]] and [[BDNF]] functional genotypes.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Aniline Compounds
* Anisotropy
* Autopsy
* Brain
* Brain-Derived Neurotrophic Factor
* Cohort Studies
* Epistasis, Genetic
* Ethylene Glycols
* Female
* Genetic Predisposition to Disease
* Genotype
* Humans
* LDL-Receptor Related Proteins
* Magnetic Resonance Imaging
* Male
* Membrane Transport Proteins
* Polymorphism, Single Nucleotide
* Positron-Emission Tomography
|keywords=* Alzheimer's disease
* Amyloid
* BDNF
* Epistasis
* PET imaging
* RNA sequencing
* SORL1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601013
}}
{{medline-entry
|title=Association and interaction effects of Alzheimer's disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28199971
|abstract=Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the [[ABCA7]], [[APOE]], [[BIN1]], [[CASS4]], [[CD2AP]], [[CD33]], [[CELF1]], [[CLU]], [[CR1]], [[DSG2]], [[EPHA1]], [[FERMT2]], [[HLA-DRB1]], [[HLA-DRB4]], [[INPP5D]], [[MEF2C]], [[MS4A4A]], [[MS4A4E]], [[MS4A6E]], [[NME8]], [[PICALM]], [[PLD3]], [[PTK2B]], [[RIN3]], [[SLC24A4]], [[SORL1]], and [[ZCWPW1]] genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. We also analyzed the interactions between lifestyle and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to evaluate cognitive functions. Out of the 588 SNPs tested in this study, only the association between [[CASS4]]-rs911159 and cognitive aging persisted significantly (P = 2.2 x 10-5) after Bonferroni correction. Our data also showed a nominal association of cognitive aging with the SNPs in six more key AD-associated genes, including [[EPHA1]]-rs10952552, [[FERMT2]]-rs4901317, [[MEF2C]]-rs9293506, [[PLD3]]-rs11672825, [[RIN3]]-rs1885747, and [[SLC24A4]]-rs67063100 (P = 0.0018~0.0097). Additionally, we found the interactions among [[CASS4]]-rs911159, EPHA-rs10952552, [[FERMT2]]-rs4901317, [[MEF2C]]-rs9293506, or [[SLC24A4]]-rs67063100 on cognitive aging (P = 0.004~0.035). Moreover, our analysis suggested the interactions of [[SLC24A4]]-rs67063100 or [[MEF2C]]-rs9293506 with lifestyle such as alcohol consumption, smoking status, physical activity, or social support on cognitive aging (P = 0.008~0.041). Our study indicates that the AD-associated genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-lifestyle interactions.
|mesh-terms=* Age Factors
* Aged
* Alleles
* Alzheimer Disease
* Cognitive Aging
* Epistasis, Genetic
* Female
* Gene-Environment Interaction
* Genetic Association Studies
* Genetic Predisposition to Disease
* Humans
* Life Style
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Risk Factors
* Taiwan
|keywords=* Alzheimer’s diseases
* Gerotarget
* Mini-Mental State Examination
* cognitive aging
* gene-gene and gene-lifestyle interactions
* single nucleotide polymorphisms
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421828
}}
{{medline-entry
|title=[[SORL1]] rs1699102 polymorphism modulates age-related cognitive decline and gray matter volume reduction in non-demented individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27779372
|abstract=[[SORL1]] rs1699102 is associated with the risk of late-onset Alzheimer's disease. However, the effects of this single nucleotide polymorphism on cognition and brain structure during normal aging are unclear. This study aimed to examine the effects of the rs1699102 polymorphism on age-related cognitive decline and cortical gray matter reduction in the Chinese Han population. A total of 780 non-demented adults completed a battery of neuropsychological tests. High-resolution T1-weighted structural magnetic resonance imaging data from 89 of these subjects were also collected using a Siemens Trio 3.0 Tesla scanner. The T allele carriers displayed an accelerated age-related change in episodic memory and processing speed tests relative to the CC genotype. A similar pattern was observed in the age-related gray matter volume (GMV) reduction of the right middle temporal pole. The GMV in this region was significantly positively correlated with the episodic memory scores. The [[SORL1]] gene rs1699102 polymorphism has been found to be associated with age-related cognitive decline and GMV reduction of the right middle temporal pole in older adults. These findings elucidate how the [[SORL1]] variants shape the neural system to modulate age-related cognitive decline and support the hypothesis that [[SORL1]] may represent a candidate gene for late-onset Alzheimer's disease.
|mesh-terms=* Aged
* Aging
* Alleles
* Brain
* Cognition
* Cognitive Dysfunction
* Female
* Genotype
* Gray Matter
* Humans
* LDL-Receptor Related Proteins
* Magnetic Resonance Imaging
* Male
* Membrane Transport Proteins
* Middle Aged
* Neuropsychological Tests
* Organ Size
* Polymorphism, Single Nucleotide
|keywords=* 
SORL1

* chinese
* cognitive decline
* gray matter volume
* non-demented elderly
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177470
}}
{{medline-entry
|title=Sex-specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27535807
|abstract=Developmental lead (Pb) exposure is suggested in laboratory studies to be a trigger for neurodegenerative diseases such as Alzheimer's disease (AD). Sortilin-related receptor, L (DLR class) A repeats-containing ([[SORL1]]) is a recently identified AD genetic risk factor. [[SORL1]] has limited characterization in vertebrate models in comparison to other AD genetic risk factors. To characterize [[SORL1]] further, protein sequence homology between humans, mice and zebrafish was analyzed and showed conservation of functional repeats and domain orientation. Next, spatial expression of sorl1 in zebrafish larvae was completed and diffuse expression in neural tissue that was not restricted to the brain was observed. Influences of sex and age on quantitative expression of sorl1 in the brain of adult zebrafish were then assessed. Sex-specific alteration of sorl1 expression transpired during the aging process in females. The zebrafish was then utilized to investigate the impacts of a 100 ppb embryonic Pb exposure on sorl1 expression and other known AD genetic risk factors. Sex-specific quantitative gene expression analysis was completed with adult zebrafish brain to compare those developmentally exposed to Pb or a control treatment, but no significant difference in sorl1 expression or other AD genetic risk factors was observed. Overall, this study provided characterization of sorl1 with changes in brain expression during aging being female-specific. This finding is in agreement with females being more prone to the onset of AD, but analysis of additional AD genetic risk factors is needed to facilitate our understanding of the impact of a 100 ppb embryonic Pb exposure. Copyright © 2016 John Wiley