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  1. Article ; Online: Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls.

    Stevenson-Hoare, Joshua / Leonenko, Ganna / Escott-Price, Valentina

    BMC public health

    2023  Volume 23, Issue 1, Page(s) 804

    Abstract: Background: Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan. Previous work has only examined the benefits of metformin over periods of less than ten years, which may ...

    Abstract Background: Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan. Previous work has only examined the benefits of metformin over periods of less than ten years, which may not be long enough to capture the true effect of this medication on longevity.
    Methods: We searched medical records for Wales, UK, using the Secure Anonymised Information Linkage dataset for type 2 diabetes patients treated with metformin (N = 129,140) and sulphonylurea (N = 68,563). Non-diabetic controls were matched on sex, age, smoking, and history of cancer and cardiovascular disease. Survival analysis was performed to examine survival time after first treatment, using a range of simulated study periods.
    Findings: Using the full twenty-year period, we found that type 2 diabetes patients treated with metformin had shorter survival time than matched controls, as did sulphonylurea patients. Metformin patients had better survival than sulphonylurea patients, controlling for age. Within the first three years, metformin therapy showed a benefit over matched controls, but this reversed after five years of treatment.
    Interpretation: While metformin does appear to confer benefits to longevity in the short term, these initial benefits are outweighed by the effects of type 2 diabetes when patients are observed over a period of up to twenty years. Longer study periods are therefore recommended for studying longevity and healthy lifespan.
    Evidence before this study: Work examining the non-diabetes outcomes of metformin therapy has suggested that there metformin has a beneficial effect on longevity and healthy lifespan. Both clinical trials and observational studies broadly support this hypothesis, but tend to be limited in the length of time over which they can study patients or participants.
    Added value of this study: By using medical records we are able to study individuals with Type 2 diabetes over a period of two decades. We are also able to account for the effects of cancer, cardiovascular disease, hypertension, deprivation, and smoking on longevity and survival time following treatment.
    Implications of all the available evidence: We confirm that there is an initial benefit to longevity of metformin therapy, but this benefit does not outweigh the negative effect on longevity of diabetes. Therefore, we suggest that longer study periods are required for inference to be made about longevity in future research.
    MeSH term(s) Humans ; Metformin/therapeutic use ; Diabetes Mellitus, Type 2/drug therapy ; Hypoglycemic Agents/therapeutic use ; Cardiovascular Diseases/chemically induced ; Longevity ; Sulfonylurea Compounds/adverse effects
    Chemical Substances Metformin (9100L32L2N) ; Hypoglycemic Agents ; Sulfonylurea Compounds
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041338-5
    ISSN 1471-2458 ; 1471-2458
    ISSN (online) 1471-2458
    ISSN 1471-2458
    DOI 10.1186/s12889-023-15764-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model.

    Martin Flores, Nuria / Podpolny, Marina / McLeod, Faye / Workman, Isaac / Crawford, Karen / Ivanov, Dobril / Leonenko, Ganna / Escott-Price, Valentina / Salinas, Patricia C

    eLife

    2024  Volume 12

    Abstract: Increasing evidence supports a role for deficient Wnt signaling in Alzheimer's disease (AD). Studies reveal that the secreted Wnt antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques in AD patients. Here, we investigate the contribution of DKK3 to ...

    Abstract Increasing evidence supports a role for deficient Wnt signaling in Alzheimer's disease (AD). Studies reveal that the secreted Wnt antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques in AD patients. Here, we investigate the contribution of DKK3 to synapse integrity in healthy and AD brains. Our findings show that DKK3 expression is upregulated in the brains of AD subjects and that DKK3 protein levels increase at early stages in the disease. In hAPP-J20 and hAPP
    MeSH term(s) Animals ; Humans ; Mice ; Alzheimer Disease/genetics ; Biological Transport ; Disease Models, Animal ; Down-Regulation ; Plaque, Amyloid ; Synapses ; Adaptor Proteins, Signal Transducing/genetics
    Chemical Substances Dkk3 protein, mouse ; Adaptor Proteins, Signal Transducing
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.89453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dementias Platform UK: Bringing genetics into life.

    Leonenko, Ganna / Bauermeister, Sarah / Ghanti, Dipanwita / Stevenson-Hoare, Joshua / Simmonds, Emily / Brookes, Keeley / Morgan, Kevin / Chaturvedi, Nishi / Elliott, Paul / Thomas, Alan / Wareham, Nicholas / Gallacher, John / Escott-Price, Valentina

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2024  

    Abstract: Introduction: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that ... ...

    Abstract Introduction: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data.
    Methods: For genetic data processing, pipelines were generated to perform quality control analysis, genetic imputation, and polygenic risk score (PRS) derivation with six genome-wide association studies of neurodegenerative diseases. Pipelines were applied to five cohorts.
    Discussion: The data processing pipelines, research-ready imputed genetic data, and PRS scores are now available on the DPUK platform and can be accessed upon request though the DPUK application process. Harmonizing genome-wide data for multiple datasets increases scientific opportunity and allows the wider research community to access and process data at scale and pace.
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Defining functional variants associated with Alzheimer's disease in the induced immune response.

    Harwood, Janet C / Leonenko, Ganna / Sims, Rebecca / Escott-Price, Valentina / Williams, Julie / Holmans, Peter

    Brain communications

    2021  Volume 3, Issue 2, Page(s) fcab083

    Abstract: Defining the mechanisms involved in the aetiology of Alzheimer's disease from genome-wide association studies alone is challenging since Alzheimer's disease is polygenic and most genetic variants are non-coding. Non-coding Alzheimer's disease risk ... ...

    Abstract Defining the mechanisms involved in the aetiology of Alzheimer's disease from genome-wide association studies alone is challenging since Alzheimer's disease is polygenic and most genetic variants are non-coding. Non-coding Alzheimer's disease risk variants can influence gene expression by affecting miRNA binding and those located within enhancers and within CTCF sites may influence gene expression through alterations in chromatin states. In addition, their function can be cell-type specific. They can function specifically in microglial enhancers thus affecting gene expression in the brain. Hence, transcriptome-wide association studies have been applied to test the genetic association between disease risk and cell-/tissue-specific gene expression. Many Alzheimer's disease-associated loci are involved in the pathways of the innate immune system. Both microglia, the primary immune cells of the brain, and monocytes which can infiltrate the brain and differentiate into activated macrophages, have roles in neuroinflammation and β-amyloid clearance through phagocytosis. In monocytes the function of regulatory variants can be context-specific after immune stimulation. To dissect the variants associated with Alzheimer's disease in the context of monocytes, we utilized data from naïve monocytes and following immune stimulation
    Language English
    Publishing date 2021-04-19
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcab083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Identifying individuals with high risk of Alzheimer's disease using polygenic risk scores.

    Leonenko, Ganna / Baker, Emily / Stevenson-Hoare, Joshua / Sierksma, Annerieke / Fiers, Mark / Williams, Julie / de Strooper, Bart / Escott-Price, Valentina

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 4506

    Abstract: Polygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, ... ...

    Abstract Polygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals' scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals' scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.
    MeSH term(s) Alleles ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Case-Control Studies ; Gene Frequency ; Genetics, Population/methods ; Genetics, Population/statistics & numerical data ; Genome-Wide Association Study/methods ; Genome-Wide Association Study/statistics & numerical data ; Genotype ; Humans ; Multifactorial Inheritance/genetics ; Polymorphism, Single Nucleotide ; Reproducibility of Results ; Risk Assessment/methods ; Risk Assessment/statistics & numerical data ; Risk Factors ; Sensitivity and Specificity
    Chemical Substances Apolipoproteins E
    Language English
    Publishing date 2021-07-23
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-24082-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cognitive Decline in Alzheimer's Disease Is Not Associated with APOE.

    Katzourou, Ioanna / Leonenko, Ganna / Ivanov, Dobril / Meggy, Alun / Marshall, Rachel / Sims, Rebecca / Williams, Julie / Holmans, Peter / Escott-Price, Valentina

    Journal of Alzheimer's disease : JAD

    2021  Volume 84, Issue 1, Page(s) 141–149

    Abstract: Background: The rate of cognitive decline in Alzheimer's disease (AD) has been found to vary widely between individuals, with numerous factors driving this heterogeneity.: Objective: This study aimed to compute a measure of cognitive decline in ... ...

    Abstract Background: The rate of cognitive decline in Alzheimer's disease (AD) has been found to vary widely between individuals, with numerous factors driving this heterogeneity.
    Objective: This study aimed to compute a measure of cognitive decline in patients with AD based on clinical information and to utilize this measure to explore the genetic architecture of cognitive decline in AD.
    Methods: An in-house cohort of 616 individuals, hereby termed the Cardiff Genetic Resource for AD, as well as a subset of 577 individuals from the publicly available ADNI dataset, that have been assessed at multiple timepoints, were used in this study. Measures of cognitive decline were computed using various mixed effect linear models of Mini-Mental State Examination (MMSE). After an optimal model was selected, a metric of cognitive decline for each individual was estimated as the random slope derived from this model. This metric was subsequently used for testing the association of cognitive decline with apolipoprotein E (APOE) genotype.
    Results: No association was found between the number of APOEɛ2 or ɛ4 alleles and the rate of cognitive decline in either of the datasets examined.
    Conclusion: Further exploration is required to uncover possible genetic variants that affect the rate of decline in patients with AD.
    MeSH term(s) Aged, 80 and over ; Alleles ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Cognitive Dysfunction/psychology ; Cohort Studies ; Female ; Genotype ; Humans ; Longitudinal Studies ; Male ; Mental Status and Dementia Tests/statistics & numerical data
    Chemical Substances Apolipoproteins E
    Language English
    Publishing date 2021-09-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-210685
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  7. Article ; Online: What does heritability of Alzheimer's disease represent?

    Baker, Emily / Leonenko, Ganna / Schmidt, Karl Michael / Hill, Matthew / Myers, Amanda J / Shoai, Maryam / de Rojas, Itziar / Tesi, Niccoló / Holstege, Henne / van der Flier, Wiesje M / Pijnenburg, Yolande A L / Ruiz, Agustin / Hardy, John / van der Lee, Sven / Escott-Price, Valentina

    PloS one

    2023  Volume 18, Issue 4, Page(s) e0281440

    Abstract: Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the ... ...

    Abstract Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability.
    Methods: We compute heritability in five large independent cohorts (N = 7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set.
    Results: SNP-based heritability of late onset Alzheimer's disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD = 8%] on average when the APOE region is excluded and an additional 1% [SD = 3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts.
    Conclusion: The heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.
    MeSH term(s) Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Alzheimer Disease/genetics ; Genetic Loci ; Polymorphism, Single Nucleotide ; Apolipoproteins E/genetics
    Chemical Substances Apolipoproteins E
    Language English
    Publishing date 2023-04-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0281440
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  8. Article ; Online: Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease.

    Stevenson-Hoare, Joshua / Heslegrave, Amanda / Leonenko, Ganna / Fathalla, Dina / Bellou, Eftychia / Luckcuck, Lauren / Marshall, Rachel / Sims, Rebecca / Morgan, Bryan Paul / Hardy, John / de Strooper, Bart / Williams, Julie / Zetterberg, Henrik / Escott-Price, Valentina

    Brain : a journal of neurology

    2022  Volume 146, Issue 2, Page(s) 690–699

    Abstract: Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. ...

    Abstract Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer's disease with biomarkers rather than clinical assessment, we assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer's disease instead of the risk of dementia. In a cohort of Alzheimer's disease cases [n = 1439, mean age 68 years (standard deviation = 8.2)] and screened controls [n = 508, mean age 82 years (standard deviation = 6.8)], we measured plasma concentrations of the 40 and 42 amino acid-long amyloid-β (Aβ) fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) using state-of-the-art Single molecule array (Simoa) technology. We tested the relationships between the biomarkers and Alzheimer's disease genetic risk, age at onset and disease duration. We also conducted a genome-wide association study for association of disease risk genes with these biomarkers. The prediction accuracy of Alzheimer's disease clinical diagnosis by the combination of all biomarkers, APOE and polygenic risk score reached area under receiver operating characteristic curve (AUC) = 0.81, with the most significant contributors being ε4, Aβ40 or Aβ42, GFAP and NfL. All biomarkers were significantly associated with age in cases and controls (P < 4.3 × 10-5). Concentrations of the Aβ-related biomarkers in plasma were significantly lower in cases compared with controls, whereas other biomarker levels were significantly higher in cases. In the case-control genome-wide analyses, APOE-ε4 was associated with all biomarkers (P = 0.011-4.78 × 10-8), except NfL. No novel genome-wide significant single nucleotide polymorphisms were found in the case-control design; however, in a case-only analysis, we found two independent genome-wide significant associations between the Aβ42/Aβ40 ratio and WWOX and COPG2 genes. Disease prediction modelling by the combination of all biomarkers indicates that the variance attributed to P-tau181 is mostly captured by APOE-ε4, whereas Aβ40, Aβ42, GFAP and NfL biomarkers explain additional variation over and above APOE. We identified novel plausible genome wide-significant genes associated with Aβ42/Aβ40 ratio in a sample which is 50 times smaller than current genome-wide association studies in Alzheimer's disease.
    MeSH term(s) Humans ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Genome-Wide Association Study ; Amyloid beta-Peptides ; Biomarkers ; Amino Acids/genetics ; Apolipoproteins E/genetics ; tau Proteins/genetics ; Peptide Fragments
    Chemical Substances Amyloid beta-Peptides ; Biomarkers ; Amino Acids ; Apolipoproteins E ; tau Proteins ; Peptide Fragments
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awac128
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  9. Article ; Online: Golgi apparatus, endoplasmic reticulum and mitochondrial function implicated in Alzheimer's disease through polygenic risk and RNA sequencing.

    Crawford, Karen / Leonenko, Ganna / Baker, Emily / Grozeva, Detelina / Lan-Leung, Benoit / Holmans, Peter / Williams, Julie / O'Donovan, Michael C / Escott-Price, Valentina / Ivanov, Dobril K

    Molecular psychiatry

    2022  Volume 28, Issue 3, Page(s) 1327–1336

    Abstract: Polygenic risk scores (PRS) have been widely adopted as a tool for measuring common variant liability and they have been shown to predict lifetime risk of Alzheimer's disease (AD) development. However, the relationship between PRS and AD pathogenesis is ... ...

    Abstract Polygenic risk scores (PRS) have been widely adopted as a tool for measuring common variant liability and they have been shown to predict lifetime risk of Alzheimer's disease (AD) development. However, the relationship between PRS and AD pathogenesis is largely unknown. To this end, we performed a differential gene-expression and associated disrupted biological pathway analyses of AD PRS vs. case/controls in human brain-derived cohort sample (cerebellum/temporal cortex; MayoRNAseq). The results highlighted already implicated mechanisms: immune and stress response, lipids, fatty acids and cholesterol metabolisms, endosome and cellular/neuronal death, being disrupted biological pathways in both case/controls and PRS, as well as previously less well characterised processes such as cellular structures, mitochondrial respiration and secretion. Despite heterogeneity in terms of differentially expressed genes in case/controls vs. PRS, there was a consensus of commonly disrupted biological mechanisms. Glia and microglia-related terms were also significantly disrupted, albeit not being the top disrupted Gene Ontology terms. GWAS implicated genes were significantly and in their majority, up-regulated in response to different PRS among the temporal cortex samples, suggesting potential common regulatory mechanisms. Tissue specificity in terms of disrupted biological pathways in temporal cortex vs. cerebellum was observed in relation to PRS, but limited tissue specificity when the datasets were analysed as case/controls. The largely common biological mechanisms between a case/control classification and in association with PRS suggests that PRS stratification can be used for studies where suitable case/control samples are not available or the selection of individuals with high and low PRS in clinical trials.
    MeSH term(s) Humans ; Alzheimer Disease/genetics ; Risk Factors ; Multifactorial Inheritance ; Mitochondria/genetics ; Endoplasmic Reticulum ; Golgi Apparatus ; Sequence Analysis, RNA ; Genome-Wide Association Study ; Genetic Predisposition to Disease
    Language English
    Publishing date 2022-12-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-022-01926-8
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  10. Article ; Online: Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis.

    Bracher-Smith, Matthew / Leonenko, Ganna / Baker, Emily / Crawford, Karen / Graham, Andrew C / Salih, Dervis A / Howell, Brian W / Hardy, John / Escott-Price, Valentina

    Neurobiology of aging

    2022  Volume 119, Page(s) 67–76

    Abstract: The APOE-ε4 allele is known to predispose to amyloid deposition and consequently is strongly associated with Alzheimer's disease (AD) risk. There is debate as to whether the APOE gene accounts for all genetic variation of the APOE locus. Another question ...

    Abstract The APOE-ε4 allele is known to predispose to amyloid deposition and consequently is strongly associated with Alzheimer's disease (AD) risk. There is debate as to whether the APOE gene accounts for all genetic variation of the APOE locus. Another question which remains is whether APOE-ε4 carriers have other genetic factors influencing the progression of amyloid positive individuals to AD. We conducted a genome-wide association study in a sample of 5,390 APOE-ε4 homozygous (ε4ε4) individuals (288 cases and 5102 controls) aged 65 or over in the UK Biobank. We found no significant associations of SNPs in the APOE locus with AD in the sample of ε4ε4 individuals. However, we identified a novel genome-wide significant locus associated to AD, mapping to DAB1 (rs112437613, OR = 2.28, CI = 1.73-3.01, p = 5.4 × 10
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Apolipoprotein E4/genetics ; Genome-Wide Association Study ; Genotype ; Homozygote ; Humans ; Nerve Tissue Proteins/genetics ; Polymorphism, Single Nucleotide/genetics ; Reelin Protein/genetics ; Signal Transduction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Apolipoprotein E4 ; DAB1 protein, human ; Nerve Tissue Proteins ; Reelin Protein ; RELN protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2022-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2022.07.009
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