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  1. Article ; Online: Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS).

    Patel, Ruhee / Cosentino, Stephanie / Zheng, Esther Zhiwei / Schupf, Nicole / Barral, Sandra / Feitosa, Mary / Andersen, Stacy L / Sebastiani, Paola / Ukraintseva, Svetlana / Christensen, Kaare / Zmuda, Joseph / Thyagarajan, Bharat / Gu, Yian

    Brain, behavior, & immunity - health

    2024  Volume 37, Page(s) 100746

    Abstract: Background and objectives: We previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and ... ...

    Abstract Background and objectives: We previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and without EM (non-EM) differ in systemic inflammation status and trajectory.
    Methods: The current study included 4333 participants of the multi-center Long Life Family Study (LLFS). LLFS families were classified as EM (556 individuals from 28 families) or non-EM (3777 individuals from 416 families), with 2 or more offspring exhibiting exceptional memory performance (i.e. having baseline composite z-score representing immediate and delayed story memory being 1.5 SD above the mean in the nondemented offspring sample) considered as EM. Blood samples from baseline were used to measure inflammatory biomarkers including total white blood cell (WBC) and its subtypes (neutrophils, lymphocytes, monocytes) count, platelet count, high sensitivity C-reactive protein, and interleukin-6. Generalized linear models were used to examine cross-sectional differences in inflammatory biomarkers at baseline. In a sub-sample of 2227 participants (338 subjects from 24 EM families and 1889 from 328 non-EM families) with repeated measures of immune cell counts, we examined whether the rate of biomarker change differed between EM and non-EM families. All models were adjusted for family size, relatedness, age, sex, education, field center, APOE genotype, and body mass index.
    Results: LLFS participants from EM families had a marginally higher monocyte count at baseline (b = 0.028, SE = 0.0110, p = 0.010) after adjusting for age, sex, education, and field site, particularly in men (p < 0.0001) but not in women (p = 0.493) (p-interaction = 0.003). Over time, monocyte counts increased (p < 0.0001) in both EM and non-EM families, while lymphocytes and platelet counts decreased over time in the non-EM families (p < 0.0001) but not in the EM families. After adjusting for multiple variables, there was no significant difference in biomarker change over time between the EM and non-EM families.
    Discussion: Compared with non-EM families, EM families had significantly higher monocyte count at baseline but had similar change over time. Our study suggests that differences in monocyte counts may be a pathway through which EM emerges in some long-lived families, especially among men.
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3546
    ISSN (online) 2666-3546
    DOI 10.1016/j.bbih.2024.100746
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: MEF2C

    Sunderaraman, Preeti / Cosentino, Stephanie / Schupf, Nicole / Manly, Jennifer / Gu, Yian / Barral, Sandra

    Frontiers in genetics

    2021  Volume 12, Page(s) 642327

    Abstract: Objectives: Myocyte Enhancer Factor 2C (: Method: Participants from two ethnic groups, Non-Hispanic White (NHW; : Results: Single nucleotide polymorphisms (SNP) variants in the : Discussion: MEF2C variant-cognitive associations shed light on an ...

    Abstract Objectives: Myocyte Enhancer Factor 2C (
    Method: Participants from two ethnic groups, Non-Hispanic White (NHW;
    Results: Single nucleotide polymorphisms (SNP) variants in the
    Discussion: MEF2C variant-cognitive associations shed light on an apparent role for
    Language English
    Publishing date 2021-07-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.642327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Association between late maternal age and age-related endophenotypes in the Long Life Family Study.

    Barral, Sandra / Andersen, Stacy L / Perls, Thomas T / Bae, Harold / Sebastiani, Paola / Christensen, Kaare / Thyagarajan, Bharat / Lee, Joseph / Schupf, Nicole

    Neuroscience letters

    2022  Volume 784, Page(s) 136737

    Abstract: Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging ... ...

    Abstract Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibit healthier endophenotype profiles compared to younger mothers. The association between maternal age and age-related endophenotypes previously derived in LLFS was assessed using Generalized Estimating Equations to adjust for relatedness. The quartiles of the maternal age at last childbirth were modeled as the independent variables. Univariate analyses tested the association between maternal age at last childbirth and age at clinical assessment, education, field center, Apolipoprotein E (APOE) genotype, depression, stress, smoking and successful pregnancies. Only the variables significantly associated in the univariate analyses were considered in secondary multivariate analyses. Univariate analyses showed that compared to older mothers (age at last birth ≥35), mothers 30 years old or younger at last childbirth are less educated (12 ± 3 years versus 13 ± 3 years) and have a higher frequency of smoking (9% versus 3% for maternal age ≥35). Results showed that older mothers (age at last birth ≥31-34 or ≥ 35) demonstrated significantly better cognitive profiles (p = 0.017 and p = 0.021 respectively) compared with mothers with last childbirth age ≤30. Later maternal age among women from long-life families is associated with a better cognitive profile, supporting the hypothesis that later age at childbirth may be a marker for healthy aging.
    MeSH term(s) Adult ; Educational Status ; Endophenotypes ; Female ; Humans ; Maternal Age ; Mothers ; Pregnancy ; Smoking
    Language English
    Publishing date 2022-06-13
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2022.136737
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Emerging science of hydroxyurea therapy for pediatric sickle cell disease.

    Green, Nancy S / Barral, Sandra

    Pediatric research

    2013  Volume 75, Issue 1-2, Page(s) 196–204

    Abstract: Hydroxyurea (HU) is the sole approved pharmacological therapy for sickle cell disease (SCD). Higher levels of fetal hemoglobin (HbF) diminish deoxygenated sickle globin polymerization in vitro and clinically reduce the incidence of disease morbidities. ... ...

    Abstract Hydroxyurea (HU) is the sole approved pharmacological therapy for sickle cell disease (SCD). Higher levels of fetal hemoglobin (HbF) diminish deoxygenated sickle globin polymerization in vitro and clinically reduce the incidence of disease morbidities. Clinical and laboratory effects of HU largely result from induction of HbF expression, though to a highly variable extent. Baseline and HU-induced HbF expression are both inherited complex traits. In children with SCD, baseline HbF remains the best predictor of drug-induced levels, but this accounts for only a portion of the induction. A limited number of validated genetic loci are strongly associated with higher baseline HbF levels in SCD. For induced HbF levels, genetic approaches using candidate single-nucleotide polymorphisms (SNPs) have identified some of these same loci as being also associated with induction. However, SNP associations with induced HbF are only partially independent of baseline levels. Additional approaches to understanding the impact of HU on HbF and its other therapeutic effects on SCD include pharmacokinetic, gene expression-based, and epigenetic analyses in patients and through studies in existing murine models for SCD. Understanding the genetic and other factors underlying the variability in therapeutic effects of HU for pediatric SCD is critical for prospectively predicting good responders and for designing other effective therapies.
    MeSH term(s) Age Factors ; Anemia, Sickle Cell/blood ; Anemia, Sickle Cell/diagnosis ; Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/genetics ; Animals ; Antisickling Agents/adverse effects ; Antisickling Agents/therapeutic use ; Child ; Child, Preschool ; Fetal Hemoglobin/genetics ; Fetal Hemoglobin/metabolism ; Genetic Markers ; Genetic Predisposition to Disease ; Humans ; Hydroxyurea/adverse effects ; Hydroxyurea/therapeutic use ; Infant ; Infant, Newborn ; Phenotype ; Polymorphism, Single Nucleotide ; Risk Factors ; Treatment Outcome
    Chemical Substances Antisickling Agents ; Genetic Markers ; Fetal Hemoglobin (9034-63-3) ; Hydroxyurea (X6Q56QN5QC)
    Language English
    Publishing date 2013-11-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/pr.2013.227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.

    Xicota, Laura / Cosentino, Stephanie / Vardarajan, Badri / Mayeux, Richard / Perls, Thomas T / Andersen, Stacy L / Zmuda, Joseph M / Thyagarajan, Bharat / Yashin, Anatoli / Wojczynski, Mary K / Krinsky-McHale, Sharon / Handen, Benjamin L / Christian, Bradley T / Head, Elizabeth / Mapstone, Mark E / Schupf, Nicole / Lee, Joseph H / Barral, Sandra

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

    2024  Volume 20, Issue 4, Page(s) 2670–2679

    Abstract: Introduction: Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.: Methods: We conducted a ... ...

    Abstract Introduction: Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.
    Methods: We conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aβ) levels.
    Results: We identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10
    Discussion: MTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology.
    Highlights: Long-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.
    MeSH term(s) Humans ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Microtubule-Associated Proteins ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis
    Chemical Substances Amyloid beta-Peptides ; Microtubule-Associated Proteins ; MTUS2 protein, human
    Language English
    Publishing date 2024-02-21
    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.13718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease.

    Green, Nancy S / Barral, Sandra

    Pediatric blood & cancer

    2010  Volume 56, Issue 2, Page(s) 177–181

    Abstract: Fetal hemoglobin (HbF) levels are generally inversely proportional to severity of sickle cell disease (SCD) for given sickle phenotypes. Molecular regulation of HbF occurs through complex interactions cis and trans to the beta globin gene locus. Novel ... ...

    Abstract Fetal hemoglobin (HbF) levels are generally inversely proportional to severity of sickle cell disease (SCD) for given sickle phenotypes. Molecular regulation of HbF occurs through complex interactions cis and trans to the beta globin gene locus. Novel insights made through population-based genetic epidemiologic studies of non-anemic populations were replicated in SCD groups, despite large differences in HbF levels. Identification of the lymphoid transcription factor BCL11A as a key suppressor of HbF expression validates approaches using population genetics to study HbF expression. We review these methods and findings, and speculate on applying pharmaco-genetics to optimize hydroxyurea therapy aimed at increasing HbF.
    MeSH term(s) Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/genetics ; Antisickling Agents/therapeutic use ; Carrier Proteins/genetics ; Fetal Hemoglobin/genetics ; Gene Expression ; Gene Expression Regulation ; Humans ; Hydroxyurea/therapeutic use ; Nuclear Proteins/genetics ; Repressor Proteins
    Chemical Substances Antisickling Agents ; BCL11A protein, human ; Carrier Proteins ; Nuclear Proteins ; Repressor Proteins ; Fetal Hemoglobin (9034-63-3) ; Hydroxyurea (X6Q56QN5QC)
    Language English
    Publishing date 2010-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.22754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico.

    Arce Rentería, Miguel / Manly, Jennifer J / Vonk, Jet M J / Mejia Arango, Silvia / Michaels Obregon, Alejandra / Samper-Ternent, Rafael / Wong, Rebeca / Barral, Sandra / Tosto, Giuseppe

    Journal of the International Neuropsychological Society : JINS

    2021  Volume 28, Issue 4, Page(s) 351–361

    Abstract: Objective: To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes and investigate the impact of midlife cardiovascular risk factors on late-life MCI among the aging Mexican population.: Method: Analyses included a sample of ... ...

    Abstract Objective: To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes and investigate the impact of midlife cardiovascular risk factors on late-life MCI among the aging Mexican population.
    Method: Analyses included a sample of non-demented adults over the age of 55 living in both urban and rural areas of Mexico (N = 1807). MCI diagnosis was assigned based on a comprehensive cognitive assessment assessing the domains of memory, executive functioning, language, and visuospatial ability. The normative sample was selected by means of the robust norms approach. Cognitive impairment was defined by a 1.5-SD cut-off per cognitive domain using normative corrections for age, years of education, and sex. Risk factors included age, education, sex, rurality, depression, insurance status, workforce status, hypertension, diabetes, stroke, and heart disease.
    Results: The prevalence of amnestic MCI was 5.9%. Other MCI subtypes ranged from 4.2% to 7.7%. MCI with and without memory impairment was associated with older age (OR = 1.01 [1.01, 1.05]; OR = 1.03 [1.01, 1.04], respectively) and residing in rural areas (OR = 1.49 [1.08, 2.06]; OR = 1.35 [1.03, 1.77], respectively). Depression (OR = 1.07 [1.02, 1.12]), diabetes (OR = 1.37 [1.03, 1.82]), and years of education (OR = 0.94 [0.91, 0.97]) were associated with MCI without memory impairment. Midlife CVD increased the odds of MCI in late-life (OR = 1.76 [1.19, 2.59], which was driven by both midlife hypertension and diabetes (OR = 1.70 [1.18, 2.44]; OR = 1.88 [1.19, 2.97], respectively).
    Conclusions: Older age, depression, low education, rurality, and midlife hypertension and diabetes were associated with higher risk of late-life MCI among older adults in Mexico. Our findings suggest that the causes of cognitive impairment are multifactorial and vary by MCI subtype.
    MeSH term(s) Aged ; Cognitive Dysfunction/etiology ; Humans ; Hypertension/complications ; Hypertension/epidemiology ; Memory Disorders ; Mexico/epidemiology ; Neuropsychological Tests ; Prevalence ; Risk Factors
    Language English
    Publishing date 2021-08-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1230632-0
    ISSN 1469-7661 ; 1355-6177
    ISSN (online) 1469-7661
    ISSN 1355-6177
    DOI 10.1017/S1355617721000539
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  8. Article ; Online: Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals.

    Barral, Sandra / Reitz, Christiane / Small, Scott A / Mayeux, Richard

    Neurobiology of aging

    2014  Volume 35, Issue 12, Page(s) 2881.e7–2881.e10

    Abstract: The molecular pathways underlying age-related memory changes remain unclear. There is a substantial genetic contribution to memory performance through life span. A recent study has implicated RbAp48, which mediates its effect on age-related memory ... ...

    Abstract The molecular pathways underlying age-related memory changes remain unclear. There is a substantial genetic contribution to memory performance through life span. A recent study has implicated RbAp48, which mediates its effect on age-related memory decline by interacting with cyclic adenosine monophosphate responsive element binding protein (CREB)1 binding protein and influencing this histone acetylation pathway. To validate these findings, we tested whether genetic variants in RbAp48, CREB1, and CREBBP are associated with memory performance in 3 independent data sets consisting of 2674 cognitively healthy elderly individuals. Genetic variant rs2526690 in the CREBBP gene was significantly associated with episodic memory performance (pmeta = 3.7 × 10(-4)) in a multivariate model adjusted for age, sex, and apolipoprotein E status. Identifying genetic variants that modulate mechanisms of cognitive aging will allow identifying valid targets for therapeutic intervention.
    MeSH term(s) Acetylation ; Aging/genetics ; Aging/psychology ; CREB-Binding Protein/genetics ; Cognition/physiology ; Cohort Studies ; Cyclic AMP Response Element-Binding Protein/genetics ; Genetic Association Studies ; Histones/metabolism ; Humans ; Memory/physiology ; Memory, Episodic ; Polymorphism, Single Nucleotide/genetics ; Retinoblastoma-Binding Protein 4/genetics
    Chemical Substances CREB1 protein, human ; Cyclic AMP Response Element-Binding Protein ; Histones ; RBBP4 protein, human ; Retinoblastoma-Binding Protein 4 ; CREB-Binding Protein (EC 2.3.1.48) ; CREBBP protein, human (EC 2.3.1.48)
    Language English
    Publishing date 2014-06-28
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2014.06.024
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  9. Article: Data from a cross-sectional study on Apolipoprotein E (APOE-ε4) and snoring/sleep apnea in non-demented older adults

    Tsapanou, Angeliki / Scarmeas, Nikolaos / Gu, Yian / Manly, Jennifer / Schupf, Nicole / Stern, Yaakov / Barral, Sandra

    Data in Brief. 2015 Dec., v. 5

    2015  

    Abstract: In the present data, we provide the details of the cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP) that examined the association between Apolipoprotein E (APOE-ε4) and snoring/sleep apnea. A total of 1944 non- ... ...

    Abstract In the present data, we provide the details of the cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP) that examined the association between Apolipoprotein E (APOE-ε4) and snoring/sleep apnea. A total of 1944 non-demented older adults constituted our sample. Sleep dysfunction was measured using sleep categories derived from the Medical Outcomes Study Sleep Scale. Stratified analyses were conducted in order to examine the association between APOE-ε4 and sleep variables by ethnic group. For further analyses and enhanced discussion, see “Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults” by Tsapanou et al. (2015) [1].
    Keywords apolipoprotein E ; cross-sectional studies ; nationalities and ethnic groups ; sleep apnea
    Language English
    Dates of publication 2015-12
    Size p. 351-353.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 2786545-9
    ISSN 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2015.09.014
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Integration of GWAS and brain transcriptomic analyses in a multiethnic sample of 35,245 older adults identifies DCDC2 gene as predictor of episodic memory maintenance.

    Gao, Yizhe / Felsky, Daniel / Reyes-Dumeyer, Dolly / Sariya, Sanjeev / Rentería, Miguel Arce / Ma, Yiyi / Klein, Hans-Ulrich / Cosentino, Stephanie / De Jager, Philip L / Bennett, David A / Brickman, Adam M / Schellenberg, Gerard D / Mayeux, Richard / Barral, Sandra

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

    2021  Volume 18, Issue 10, Page(s) 1797–1811

    Abstract: Identifying genes underlying memory function will help characterize cognitively resilient and high-risk declining subpopulations contributing to precision medicine strategies. We estimated episodic memory trajectories in 35,245 ethnically diverse older ... ...

    Abstract Identifying genes underlying memory function will help characterize cognitively resilient and high-risk declining subpopulations contributing to precision medicine strategies. We estimated episodic memory trajectories in 35,245 ethnically diverse older adults representing eight independent cohorts. We conducted apolipoprotein E (APOE)-stratified genome-wide association study (GWAS) analyses and combined individual cohorts' results via meta-analysis. Three independent transcriptomics datasets were used to further interpret GWAS signals. We identified DCDC2 gene significantly associated with episodic memory (Pmeta = 3.3 x 10
    MeSH term(s) Humans ; Aged ; Memory, Episodic ; Apolipoprotein E4/genetics ; Genome-Wide Association Study ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Transcriptome ; Brain/metabolism ; Apolipoproteins E/genetics ; Microtubule-Associated Proteins
    Chemical Substances Apolipoprotein E4 ; Amyloid beta-Peptides ; Apolipoproteins E ; DCDC2 protein, human ; Microtubule-Associated Proteins
    Language English
    Publishing date 2021-12-07
    Publishing country United States
    Document type Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12524
    Database MEDical Literature Analysis and Retrieval System OnLINE

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