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View article: Aquaporin-4 polymorphisms modify the penetrance of Parkinson’s disease in <i>leucine-rich repeat kinase 2</i> carriers
Aquaporin-4 polymorphisms modify the penetrance of Parkinson’s disease in <i>leucine-rich repeat kinase 2</i> carriers Open
Background Pathogenic mutations in the leucine-rich repeat kinase-2 ( LRRK2 ) gene are the most common cause of familial Parkinson’s disease (PD). LRRK2 shows incomplete penetrance, yet the biological factors influencing disease expression…
View article: Publisher Correction: Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes
Publisher Correction: Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes Open
View article: Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium
Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium Open
INTRODUCTION We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition.…
View article: Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals
Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals Open
View article: Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages
Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages Open
Social behaviour is a heritable, context-dependent trait that changes across social settings and development, influencing wellbeing and mental health. We present the first genome-wide meta-regression study of social behaviour from infancy …
View article: The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging
The Global Neurodegeneration Proteomics Consortium: biomarker and drug target discovery for common neurodegenerative diseases and aging Open
View article: Why do we get sick? Genetic evidence for evolutionary trade-offs between fertility, longevity, and disease
Why do we get sick? Genetic evidence for evolutionary trade-offs between fertility, longevity, and disease Open
The persistence of genetic variants that increase susceptibility to complex diseases poses an evolutionary paradox: despite their detrimental health effects, these variants are not eliminated by natural selection. Life-history theory propo…
View article: Neuroimaging-derived biological brain age and its associations with glial reactivity and synaptic dysfunction cerebrospinal fluid biomarkers
Neuroimaging-derived biological brain age and its associations with glial reactivity and synaptic dysfunction cerebrospinal fluid biomarkers Open
Magnetic resonance Imaging (MRI)-derived brain-age prediction is a promising biomarker of biological brain aging. Accelerated brain aging has been found in Alzheimer's disease (AD) and other neurodegenerative diseases. However, no previous…
View article: Large-scale Plasma Proteomic Profiling Unveils Novel Diagnostic Biomarkers and Pathways for Alzheimer's Disease
Large-scale Plasma Proteomic Profiling Unveils Novel Diagnostic Biomarkers and Pathways for Alzheimer's Disease Open
Alzheimer disease (AD) is a complex neurodegenerative disorder. Proteomic studies have been instrumental in identifying AD-related proteins present in the brain, cerebrospinal fluid, and plasma. This study comprehensively examined 6,905 pl…
View article: Compositional brain scores capture Alzheimer's disease–specific structural brain patterns along the disease continuum
Compositional brain scores capture Alzheimer's disease–specific structural brain patterns along the disease continuum Open
INTRODUCTION Traditional multivariate methods for neuroimaging studies overlook the interdependent relationship between brain features. This study addresses this gap by analyzing relative brain volumetric patterns to capture how Alzheimer'…
View article: Genetic drivers of hippocampal atrophy highlight the role of APOE functional variants and AD polygenicity in Mild Cognitive Impairment
Genetic drivers of hippocampal atrophy highlight the role of APOE functional variants and AD polygenicity in Mild Cognitive Impairment Open
View article: Shorter leukocyte telomere length is associated with distinct CSF biomarker dynamics across early AD stages in at-risk individuals
Shorter leukocyte telomere length is associated with distinct CSF biomarker dynamics across early AD stages in at-risk individuals Open
INTRODUCTION Telomere length (TL) is a hallmark of biological aging. Shorter TL has been linked to an increased risk of Alzheimer’s disease (AD), but its role in AD pathophysiology remains unclear. This study investigates the relationship …
View article: Associations between AD polygenic risk scores and global amyloid deposition in the European AMYPAD consortium
Associations between AD polygenic risk scores and global amyloid deposition in the European AMYPAD consortium Open
Background Published data have highlighted associations between Alzheimer’s disease (AD) susceptibility loci and AD‐related brain changes. The amyloid imaging to prevent AD (AMYPAD) consortium is a European collaboration consisting of seve…
View article: Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers
Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers Open
Background Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD …
View article: Exploring Sex‐Specific Accelerated Hippocampal Atrophy Across AD Stages beyond APOE‐e4 Assessment in Genetic Risk Evaluation
Exploring Sex‐Specific Accelerated Hippocampal Atrophy Across AD Stages beyond APOE‐e4 Assessment in Genetic Risk Evaluation Open
Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic pred…
View article: Genetic proxies for predicting plasma protein levels reveal TIMP2 role in human cognitive performance
Genetic proxies for predicting plasma protein levels reveal TIMP2 role in human cognitive performance Open
Background Murine studies have identified blood proteins that influence brain aging, but translating these findings to humans remains challenging. We used an innovative approach to investigate whether genetically predicted blood levels of …
View article: Performance of plasma NTK biomarkers to detect amyloid‐β pathology in cognitively unimpaired individuals at risk of Alzheimer’s disease
Performance of plasma NTK biomarkers to detect amyloid‐β pathology in cognitively unimpaired individuals at risk of Alzheimer’s disease Open
Background Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amy…
View article: Exploring sex‐specific accelerated hippocampal atrophy across AD stages beyond <i>APOE‐ε4</i> assessment in genetic risk evaluation
Exploring sex‐specific accelerated hippocampal atrophy across AD stages beyond <i>APOE‐ε4</i> assessment in genetic risk evaluation Open
Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic pred…
View article: Longer leukocyte telomere length is associated with lower markers of early Alzheimer's disease pathology, astrocytic reactivity, and synaptic dysfunction
Longer leukocyte telomere length is associated with lower markers of early Alzheimer's disease pathology, astrocytic reactivity, and synaptic dysfunction Open
Background Leukocyte telomere length (LTL) serves as a proxy for tissue‐specific TL and peripheral immune aging. Its association with aging‐related brain endophenotypes, cognitive functioning, and Alzheimer's disease (AD) risk is establish…
View article: Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers
Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers Open
Background Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD …
View article: Exploring Sex‐Specific Accelerated Hippocampal Atrophy Across AD Stages beyond APOE‐e4 Assessment in Genetic Risk Evaluation
Exploring Sex‐Specific Accelerated Hippocampal Atrophy Across AD Stages beyond APOE‐e4 Assessment in Genetic Risk Evaluation Open
Background Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer’s disease (AD). In this study, we investigated whether genetic pred…
View article: Genetic predisposition to AD and inflammation determine vulnerable brain regions to air pollution
Genetic predisposition to AD and inflammation determine vulnerable brain regions to air pollution Open
Background The detrimental effects of air pollution on health are well‐documented, yet its impact on brain structure in the early asymptomatic stages of Alzheimer’s disease (AD) remains under‐explored. This study investigated the relations…
View article: From AMYPAD to Euro‐PAD: creating a multi‐cohort preclinical database to model onset of Alzheimer’s disease
From AMYPAD to Euro‐PAD: creating a multi‐cohort preclinical database to model onset of Alzheimer’s disease Open
Background The emergence of disease‐modifying drug therapies is expected to revolutionize the field of Alzheimer's disease (AD). Recent results from anti‐amyloid clinical trials highlight the importance of early identification and accurate…
View article: Genetic predisposition to AD and inflammation determine vulnerable brain regions to air pollution
Genetic predisposition to AD and inflammation determine vulnerable brain regions to air pollution Open
Background The detrimental effects of air pollution on health are well‐documented, yet its impact on brain structure in the early asymptomatic stages of Alzheimer’s disease (AD) remains under‐explored. This study investigated the relations…
View article: Sex-specific neuroinflammatory responses to air pollution mediates cognitive performance in cognitively unimpaired individuals at risk of Alzheimer’s dementia
Sex-specific neuroinflammatory responses to air pollution mediates cognitive performance in cognitively unimpaired individuals at risk of Alzheimer’s dementia Open
Background A growing body of research links environmental factors with neurodegeneration and premature mortality. However, the biological mechanisms through which pollutants affect early Alzheimer’s disease (AD) pathology in asymptomatic s…
View article: Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non‐demented individuals
Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non‐demented individuals Open
INTRODUCTION Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine. METHODS We computed pat…
View article: Polygenic proxies of age-related plasma protein levels reveal TIMP2 role in cognitive performance
Polygenic proxies of age-related plasma protein levels reveal TIMP2 role in cognitive performance Open
Several studies have identified blood proteins that influence brain aging performance in mice, yet translating these findings to humans remains challenging. Here we found that higher predicted plasma levels of Tissue Inhibitor of Metallopr…
View article: CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease
CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease Open
INTRODUCTION We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3‐like protein 1 (YKL‐40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and pla…
View article: Structural Brain Differences in the Alzheimer’s Disease Continuum: Insights Into the Heterogeneity From a Large Multisite Neuroimaging Consortium
Structural Brain Differences in the Alzheimer’s Disease Continuum: Insights Into the Heterogeneity From a Large Multisite Neuroimaging Consortium Open
Diversity in data offers unique insights into the neural substrate of AD; however, harmonized processing and transparency of data collection are needed. Global collaborations should embrace the inherent heterogeneity that exists in the dat…
View article: Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer’s disease
Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer’s disease Open