Badri N. Vardarajan
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View article: Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer’s disease
Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer’s disease Open
Circulating metabolites can identify biochemical risk factors related to Alzheimer's disease (AD). We measured plasma metabolites in 1,068 participants of Caribbean Hispanic ancestry (250 patients with AD and 818 healthy controls) across 2…
View article: The Asian Cohort for Alzheimer's Disease (ACAD) Study: 2025 Update
The Asian Cohort for Alzheimer's Disease (ACAD) Study: 2025 Update Open
Background Asian Americans and Asian Canadians (ASACs) are the fastest‐growing minority group in the US and Canada, yet they are under‐representative in Alzheimer's disease (AD) research. To address the need of culturally appropriate clini…
View article: TPClust: Temporal Profile‐Guided Disease Subtyping Using High‐Dimensional Omics Data
TPClust: Temporal Profile‐Guided Disease Subtyping Using High‐Dimensional Omics Data Open
Background Alzheimer's Disease (AD) subtyping using unsupervised clustering of omics data often results in subtypes with limited clinical relevance. To address this, we developed a novel supervised clustering method integrating longitudina…
View article: Acculturation, Education, and Cognition in Older Asian Americans and Canadians: results from the Asian Cohort for Alzheimer's Disease study
Acculturation, Education, and Cognition in Older Asian Americans and Canadians: results from the Asian Cohort for Alzheimer's Disease study Open
Background Acculturation—adapting to a new culture—plays a significant role in shaping health outcomes among immigrants, including older Asian Americans and Canadians (ASACs). Education, a well‐established protective factor for cognition, …
View article: <i>APOE, ABCA7</i> , and <i>RASGEF1C</i> are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images
<i>APOE, ABCA7</i> , and <i>RASGEF1C</i> are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images Open
INTRODUCTION New methods estimate amyloid positivity onset age (EAOA) from amyloid positron emission tomography (PET). We explore the genetics of EAOA to identify molecular factors underlying the earliest Alzheimer's disease (AD) changes. …
View article: Alzheimer's Disease and concomitant pathologies in SuperAgers
Alzheimer's Disease and concomitant pathologies in SuperAgers Open
Background “SuperAgers” are oldest‐old adults (ages 80+) with memory performance resembling adults in their 50s to mid‐60s. This study assessed presence and levels of Alzheimer's disease (AD) neuropathologic change (ADNC) and concomitant n…
View article: Polygenic scores of Core 1 Alzheimer's disease biomarkers predict early cognitive and pathological change
Polygenic scores of Core 1 Alzheimer's disease biomarkers predict early cognitive and pathological change Open
INTRODUCTION Core 1 biomarkers, such as amyloid positron emission tomography, capture the earliest biological changes leading to Alzheimer's disease (AD). While APOE is a major genetic factor, the contribution of other variants to Core 1 b…
View article: P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits
P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits Open
The immune system plays a dynamic role in neurodegenerative diseases, and purinergic receptors allow immune cells to recognize neuronal signaling, cell injury, or stress. Purinergic Receptor 7 (P2RX7) can modulate inflammatory cascades, an…
View article: TPClust: Temporal Profile-Guided Subtyping Using High-Dimensional Omics Data
TPClust: Temporal Profile-Guided Subtyping Using High-Dimensional Omics Data Open
Clustering is widely used to identify subtypes in heterogeneous populations, yet most approaches rarely integrate longitudinal phenotypic trajectories with high-dimensional molecular profiles, limiting their ability to resolve biologically…
View article: CD33-CD45 Interaction Reveals a Mechanistic Link to Alzheimer’s Disease Susceptibility
CD33-CD45 Interaction Reveals a Mechanistic Link to Alzheimer’s Disease Susceptibility Open
The innate immune gene CD 33, encoding a myeloid inhibitory sialic acid-binding receptor, is associated with Alzheimer’s disease (AD) susceptibility. The AD-associated rs3865444 CC risk variant reduces splicing of the sialic acid-binding d…
View article: CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk
CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk Open
We report the results of structural, functional and genetic studies on the CD33 sialic acid- binding receptor that reveal how non-coding variants in CD33 alter risk for Alzheimer’s disease (AD). The full-length CD33 M isoform, whose expres…
View article: Polygenic Scores of Core-1 Alzheimer’s Disease Biomarkers Predict Early Cognitive and Pathological Change
Polygenic Scores of Core-1 Alzheimer’s Disease Biomarkers Predict Early Cognitive and Pathological Change Open
BACKGROUND Core-1 biomarkers, such as amyloid PET, capture the earliest biological changes leading to Alzheimer’s disease (AD). While APOE is a major genetic factor, the contribution of other variants to Core-1 biomarkers remains unclear. …
View article: Biological Age and Age Acceleration Predict Alzheimer’s Disease Plasma Biomarker Levels
Biological Age and Age Acceleration Predict Alzheimer’s Disease Plasma Biomarker Levels Open
Epigenetic clocks can predict pathological aging associated with Alzheimer’s disease (AD) risk, albeit findings are mixed regarding if clocks are predictive in blood and in non-European populations. We constructed epigenetic clocks from bl…
View article: Single-nucleus multiomics in brains from Hispanic individuals reveal<i>APOE-ε4</i>-driven disruption of focal adhesion signaling in the presence of cerebrovascular pathology
Single-nucleus multiomics in brains from Hispanic individuals reveal<i>APOE-ε4</i>-driven disruption of focal adhesion signaling in the presence of cerebrovascular pathology Open
The apolipoprotein E ε4 allele ( APOE-ε4 ) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), yet its molecular impact on cerebrovascular biology remains inconclusive, particularly in underrepresented populations…
View article: Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset
Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset Open
INTRODUCTION The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's disease and related dementias (ADRD) by integrating whole genome sequencing (WGS) with other gene…
View article: Preclinical Alzheimer's disease shows alterations in circulating neuronal‐derived extracellular vesicle microRNAs in a multiethnic cohort
Preclinical Alzheimer's disease shows alterations in circulating neuronal‐derived extracellular vesicle microRNAs in a multiethnic cohort Open
INTRODUCTION Alzheimer's disease (AD) is the leading cause of dementia, affecting around 50 million individuals worldwide. Brain‐derived extracellular vesicles (EVs) can cross the blood–brain barrier carrying neuron‐specific molecules, suc…
View article: Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study
Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study Open
HbA1c is clinically used in T2D diagnosis and monitoring. Its longitudinal change (ΔHbA1c) is associated with T2D-related aging processes and mortality. Targeted association tests under significant linkage peaks in extended families permit…
View article: Genetic Regulation of the Metabolome Differs by Sex, Alzheimer’s Disease Stage, and Plasma Biomarker Status
Genetic Regulation of the Metabolome Differs by Sex, Alzheimer’s Disease Stage, and Plasma Biomarker Status Open
We investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-assisted diagnosis of Alzheimer’s disease (AD). We computed metabolite quantitative trait lo…
View article: Rare<i>PANK2</i>Variants and Pantothenate Kinase-Associated Neurodegeneration in the Dominican Republic
Rare<i>PANK2</i>Variants and Pantothenate Kinase-Associated Neurodegeneration in the Dominican Republic Open
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurological disorder characterized by the progressive degeneration of specific regions in the brain and is invariably fatal. Several individuals in fam…
View article: <i>APOE-</i>ε4-induced Fibronectin at the blood-brain barrier is a conserved pathological mediator of disrupted astrocyte-endothelia interaction in Alzheimer’s disease
<i>APOE-</i>ε4-induced Fibronectin at the blood-brain barrier is a conserved pathological mediator of disrupted astrocyte-endothelia interaction in Alzheimer’s disease Open
Blood-brain barrier (BBB) dysfunction is a key feature of Alzheimer’s disease (AD), particularly in individuals carrying the APOE-ε4 allele. This dysfunction worsens neuroinflammation and hinders the removal of toxic proteins, such as amyl…
View article: Evaluating the association of<i>APOE</i>genotype and cognitive resilience in SuperAgers
Evaluating the association of<i>APOE</i>genotype and cognitive resilience in SuperAgers Open
INTRODUCTION “SuperAgers” are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined APOE allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperA…
View article: Rare <i>PANK2</i> variants and pantothenate-kinase-associated neurodegeneration in the Dominican Republic
Rare <i>PANK2</i> variants and pantothenate-kinase-associated neurodegeneration in the Dominican Republic Open
Pantothenate-kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurological disorder characterized by the progressive degeneration of specific regions in the brain and is invariably fatal. Several individuals in fam…