225 results found
Wagner M, Lorenz G, Volk AE, et al., 2021, Clinico-genetic findings in 509 frontotemporal dementia patients, MOLECULAR PSYCHIATRY, ISSN: 1359-4184
Kusters CDJ, Paul KC, Folle AD, et al., 2021, Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach, MOVEMENT DISORDERS, Vol: 36, Pages: 2264-2272, ISSN: 0885-3185
Shi L, Buckley NJJ, Bos I, et al., 2021, Plasma Proteomic Biomarkers Relating to Alzheimer's Disease: A Meta-Analysis Based on Our Own Studies, FRONTIERS IN AGING NEUROSCIENCE, Vol: 13, ISSN: 1663-4365
Hong S, Dobricic V, Ohlei O, et al., 2021, TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels, ALZHEIMERS & DEMENTIA, Vol: 17, Pages: 1628-1640, ISSN: 1552-5260
Nyberg L, Magnussen F, Lundquist A, et al., 2021, Educational attainment does not influence brain aging, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 118, ISSN: 0027-8424
Kronenberg G, Gertz K, Schoener J, et al., 2021, BDNF serum concentrations in 2053 participants of the Berlin Aging Study II, NEUROBIOLOGY OF AGING, Vol: 101, Pages: 221-223, ISSN: 0197-4580
Grydeland H, Sederevičius D, Wang Y, et al., 2021, Self-Reported Sleep Relates to Microstructural Hippocampal Decline in β-Amyloid Positive Adults Beyond Genetic Risk., Sleep
STUDY OBJECTIVES: A critical role linking sleep with memory decay and β-amyloid (Aβ) accumulation, two markers of Alzheimer's disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of Aβ. METHODS: Two-hundred and forty-three cognitively healthy participants, aged 19-81 years, completed the Pittsburgh Sleep Quality Index once, and 2 diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 Aβ positive. Genotyping enabled control for APOE ε4 status, and polygenic scores for sleep and AD, respectively. RESULTS: Worse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of Aβ accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD. CONCLUSIONS: Worse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of Aβ accumulation, and Aβ might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown.
Prokopenko D, Morgan SL, Mullin K, et al., 2021, Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development, ALZHEIMERS & DEMENTIA, Vol: 17, Pages: 1509-1527, ISSN: 1552-5260
Shi L, Winchester LM, Westwood S, et al., 2021, Replication study of plasma proteins relating to Alzheimer's pathology, ALZHEIMERS & DEMENTIA, Vol: 17, Pages: 1452-1464, ISSN: 1552-5260
Jones G, Trajanoska K, Santanasto AJ, et al., 2021, Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
Demuth I, Banszerus V, Drewelies J, et al., 2021, Cohort profile: follow-up of a Berlin Aging Study II (BASE-II) subsample as part of the GendAge study, BMJ OPEN, Vol: 11, ISSN: 2044-6055
Hong S, Prokopenko D, Dobricic V, et al., 2020, Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset, TRANSLATIONAL PSYCHIATRY, Vol: 10, ISSN: 2158-3188
Tijms BM, Gobom J, Reus L, et al., 2020, Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics, BRAIN, Vol: 143, Pages: 3776-3792, ISSN: 0006-8950
Walhovd KB, Fjell AM, Sorensen O, et al., 2020, Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan, NEUROLOGY-GENETICS, Vol: 6, ISSN: 2376-7839
Kusters CDJ, Paul KC, Folle AD, et al., 2020, Genetic risk scores and hallucinations in patients with Parkinson disease, NEUROLOGY-GENETICS, Vol: 6, ISSN: 2376-7839
Rieck L, Bardey F, Grenkowitz T, et al., 2020, Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia, CLINICAL GENETICS, Vol: 98, Pages: 457-467, ISSN: 0009-9163
Bertram L, Tanzi RE, 2020, Genomic mechanisms in Alzheimer's disease, BRAIN PATHOLOGY, Vol: 30, Pages: 966-977, ISSN: 1015-6305
Roehr F, Bucholtz N, Toepfer S, et al., 2020, Relationship between Lipoprotein (a) and cognitive function - Results from the Berlin Aging Study II, SCIENTIFIC REPORTS, Vol: 10, ISSN: 2045-2322
Konijnenberg E, Tijms BM, Gobom J, et al., 2020, APOE epsilon 4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease, ALZHEIMERS RESEARCH & THERAPY, Vol: 12
Fjell AM, Sederevicius D, Sneve MH, et al., 2020, Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression, CEREBRAL CORTEX, Vol: 30, Pages: 2144-2156, ISSN: 1047-3211
Prokopenko D, Hecker J, Kirchner R, et al., 2020, Identification of Novel Alzheimer's Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data, SCIENTIFIC REPORTS, Vol: 10, ISSN: 2045-2322
Wohlers I, Schulz C, Kilpert F, et al., 2020, Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines, NEUROBIOLOGY OF AGING, Vol: 86, ISSN: 0197-4580
Shi L, Winchester LM, Liu BY, et al., 2020, Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology, JOURNAL OF ALZHEIMERS DISEASE, Vol: 77, Pages: 1353-1368, ISSN: 1387-2877
Westwood S, Baird AL, Anand SN, et al., 2020, Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort, JOURNAL OF ALZHEIMERS DISEASE, Vol: 74, Pages: 213-225, ISSN: 1387-2877
Shi L, Westwood S, Baird AL, et al., 2019, Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay, ALZHEIMERS & DEMENTIA, Vol: 15, Pages: 1478-1488, ISSN: 1552-5260
Takousis P, Sadlon A, Schulz J, et al., 2019, Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid, Alzheimers & Dementia, Vol: 15, Pages: 1468-1477, ISSN: 1552-5260
INTRODUCTION: Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive. METHODS: A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty. RESULTS: Data from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10-4) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles. DISCUSSION: Our systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.
Schmidt AF, Holmes MV, Preiss D, et al., 2019, Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9, BMC Cardiovascular Disorders, Vol: 19, ISSN: 1471-2261
BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
Morgan AR, Touchard S, Leckey C, et al., 2019, Inflammatory biomarkers in Alzheimer's disease plasma, ALZHEIMERS & DEMENTIA, Vol: 15, Pages: 776-787, ISSN: 1552-5260
Kim M, Snowden S, Suvitaival T, et al., 2019, Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort, ALZHEIMERS & DEMENTIA, Vol: 15, Pages: 817-827, ISSN: 1552-5260
Schulz J, Takousis P, Wohlers I, et al., 2019, Meta-analyses identify differentially expressed microRNAs in Parkinson's disease, Annals of Neurology, Vol: 85, Pages: 835-851, ISSN: 0364-5134
Objective: MicroRNA-mediated (dys)regulation of gene expression has been implicated in Parkinson's disease (PD), although results of microRNA expression studies remain inconclusive. We aimed to identify microRNAs that show consistent differential expression across all published expression studies in PD.Mathods: We performed a systematic literature search on microRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen we performed meta-analyses across microRNAs assessed in three or more independent datasets. Meta-analyses were performed using effect-size and p-value based methods, as applicable.Results: After screening 599 publications we identified 47 datasets eligible for meta-analysis. On these, we performed 160 meta-analyses on microRNAs quantified in brain (n=125), blood (n=31), or CSF samples (n=4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted α=3.13x10-4 ) differentially expressed microRNAs in brain (n=3) and blood (n=10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p=6.37x10-5 ), hsa-miR-497-5p (p=1.35x10-4 ), and hsa-miR-133b (p=1.90x10-4 ) in brain, and with hsa-miR-221-3p (p=4.49x10-35 ), hsa-miR-214-3p (p=2.00x10-34 ), and hsa-miR-29c-3p (p=3.00x10-12 ) in blood. No significant signals were found in CSF. Analyses of GWAS data for target genes of brain microRNAs showed significant association (α=9.40x10-5 ) of genetic variants in nine loci.Interpretation: We identified several microRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.
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