
Agustin RuizFundació ACE · Research
Agustin Ruiz
M.D. Ph.D.
About
549
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Introduction
Now i am focussed in Genome Research applied to Neurodegenerative disorders
Additional affiliations
August 2011 - present
Publications
Publications (549)
Background
Emerging technologies and novel biomarker tools are transforming the field of Alzheimer’s disease, allowing for a more in‐depth exploration of biological mechanisms underpinning the disease aetio‐pathogenesis. In this context, there is growing recognition of the potential of plasma proteomics for AD risk assessment and disease characteri...
Background
Cerebrospinal fluid (CSF) is a valuable resource for the study and diagnosis of neurological diseases, but few studies have comprehensively characterized the genetic determinants of CSF protein levels that may contribute to the development of disease. These quantitative trait loci (QTL) have proven vital to identifying candidate genes fo...
Background
Precision neuroscience is emerging as a transformative approach that aims to identify the right treatment for the right patient at the right time. To enable this, it is important to move beyond the categorization of patients based on clinical symptoms towards a biological definition of disease. For Alzheimer’s disease, significant progre...
Background
Glial fibrillary acidic protein (GFAP) is an astrocytic cytoskeletal protein and a promising blood biomarker for Alzheimer's disease (AD) and other neurodegenerative diseases. To date, the genetic architecture of plasma GFAP has not been characterized. We conducted a multi‐ancestry meta‐analyses of genome‐wide association studies (GWAS)...
Background
Changes in Amyloid‐β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.
Method
We used the Somascan assay for measuring the protein levels of 7,029 analytes...
Background
Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome‐wide association studies (GWAS) and high‐throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involv...
Background
Alzheimer’s Disease (AD) is a complex disorder and much of its etiopathology is still unknown. Here, we applied dimensionality reduction methods to disentangle cyptic patterns in CSF proteomic and lipidomic data.
Method
We studied 1121 CSF samples using targeted lipidomics based on liquid chromatography (LC)‐MS/MS (mass spectrometry), g...
Background
Brain 1,2 , cerebrospinal fluid (CSF) 3,4 , and plasma 5,6 metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer’s disease (AD). However, many AD‐focused metabolomics studies profiled a relatively small number of individuals and metabolites 3–6 , especially for CSF. In addition, past studies were li...
Background
Clear sex differences exist in AD and PD. Several studies examined genetic regulations for AD phenotypes and gene expression data in a sex‐specific manner, identifying some differences between males and females. In contrasts, although proteins are final effectors of most physiological pathways and important drug targets, sex‐specific reg...
High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona re...
Background: Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are currently underdiagnosed in the community, and early detection of cognitive deficits is crucial for timely intervention. FACEmemory®, the first completely self-administered online memory test with voice recognition, has been launched as an accessible tool to detec...
Background
Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aime...
Background:
Substantial evidence supports the relationship between peripheral insulin resistance (IR) and the development of Alzheimer's disease (AD)-dementia. However, the mechanisms explaining these associations are only partly understood. We aimed to identify a metabolic signature of IR associated with the progression from mild cognitive impair...
Background
Optical coherence tomography (OCT) enables high-resolution imaging of ocular structures in health and disease. Choroid thickness (CT) is a key vascular retinal parameter that can be assessed by OCT and might be relevant in the evaluation of the vascular component of cognitive decline. We aimed to investigate CT changes in a large cohort...
Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 ne...
The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 p...
Despite the central role attributed to neuroinflammation in the etiology and pathobiology of Alzheimer's disease (AD), the direct link between levels of inflammatory mediators in blood and cerebrospinal fluid (CSF) compartments, as well as their potential implications for AD diagnosis and progression, remains inconclusive. Moreover, there is debate...
Background: Alzheimer's disease (AD) dementia and Mild Cognitive Impairment (MCI) are currently underdiagnosed in the community. Early detection of cognitive deficits is crucial for timely intervention. FACEmemory®, the first completely self-administered online memory test with voice recognition, has been launched as an accessible tool to detect su...
Objective
There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE‐Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures.
Methods
Serum and cerebrosp...
Objective
Pathological amyloid‐β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1‐42 and p181‐tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive...
Background
The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed...
Background
Alzheimer’s disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, whic...
Background
The APOE gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized.
Methods
To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brain...
A deeper understanding of the molecular processes underlying late-onset Alzheimer’s disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics in the prospective population-based Age, Gene/Environment Susceptibility–Reykjavik Study (AGES) cohort of 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years...
Background
Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD...
High-throughput proteomic platforms have a crucial role in identifying novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center B...
We conducted the largest PSP GWAS of the Iberian population to date (522 cases from 22 Spanish and Portuguese institutions). We independently replicated seven known PSP risk variants, and unveiled a novel locus in NFASC/CNTN2 after meta-analysing our results with a newly available Dutch cohort and publicly available summary statistics. These findin...
Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 protein...
Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We descr...
Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking...
INTRODUCTION
Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.
METHODS
Genome‐wide...
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To finally address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clini...
In Alzheimer s disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to ide...
Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of t...
Background:
Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers amyloid-β(Aβ) phagocytosis via TYROBP.
Objective:
To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD...
Introduction
Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in...
Background
Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber l...
The genetic basis of severe COVID-19 has been thoroughly studied and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we have conducted the larges...
Background
Advancement in screening tools accessible to the general population for the early detection of Alzheimer’s disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting decentralized clinical trials. This study delves into the application of Machine Learning (ML) techniques by l...
Background and objectives:
Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.
Methods:
We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/En...
Background
Alzheimer’s disease (AD) diagnosis relies on clinical symptoms complemented with biological biomarkers, the Amyloid Tau Neurodegeneration (ATN) framework. Small non-coding RNA (sncRNA) in the blood have emerged as potential predictors of AD. We identified sncRNA signatures specific to ATN and AD, and evaluated both their contribution to...
Background: The FACEmemory® online platform comprises a complex memory test and sociodemographic, medical, and family questions. This is the first study of a completely self-administered memory test with voice recognition, pre-tested in a memory clinic, sensitive to Alzheimer’s disease, using information and communication technologies, and offered...
Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTR...
Background
High‐throughput proteomic platforms are an useful strategy to detect novel biomarkers and pathways involved in Alzheimer’s disease (AD) development. Due to the novelty of these techniques, an extensive quality control assessment is needed to ensure the reliability of those protein measurements. In this study, we aimed to assess the repro...
Background
Recent studies have found that duplications or deletions of DNA fragments, known as copy number variants (CNVs), may play a role in missing heritability for complex human diseases.
Method
In that sense, we conducted a scan for CNVs in the GR@ACE/DEGESCO dementia dataset of Spanish population ¹ (n = 20,080 individuals using Axiom 815K Sp...
Background
Brain metabolism is critical for the pathological mechanism of neurodegeneration. However, most metabolite quantitative trait loci (MQTL) studies have used tissues other than brain or cerebrospinal fluid (CSF) and are not ideal for neurodegeneration. We therefore pursued a large‐scale brain and CSF study to identify metabolites contribut...
Background
Progressive supranuclear palsy (PSP) is a rare neurodegenerative tauopathy. We genotyped all the available histopatologically confirmed PSP cases from the Spanish National Biobank Network and patients with a probable PSP diagnosis recruited from research groups linked to the Dementia Genetics Spanish Consortium (DEGESCO). Here, we presen...
Background
Quantitative trait loci (QTL) are successful at identifying the functional gene for many loci identified through GWAS. While expression QTL (eQTL) studies robustly examine tissue‐specificity, most protein QTL (pQTL) studies have been limited to plasma. We have previously demonstrated that pQTL associations are highly tissue‐specific. Giv...
Background
Age is the strongest risk factor for dementia, including Alzheimer’s disease (AD). However, across individuals of the same chronological age there is considerable heterogeneity in rates of cognitive decline. These differences have been attributed to individual differences in age‐related biological processes, including brain protein expre...
Background
Sporadic Alzheimer’s disease (AD) is a highly heterogeneous multifactorial disease in which females have a higher risk. Among 5.3 million senior Americans diagnosed with AD, over 60% are female. Despite the well‐established sex differences, sex‐specific molecular findings in AD are still limited. We therefore examined the role of sex in...
Background
Leucine‐rich repeat kinase 2 (LRRK2) common gene variants (tagged by rs76904798) are associated with Parkinson’s disease (PD) risk. In a previous study, we found that rs76904798 was associated with CSF GRN levels, but a comprehensive unbiased analysis of associated proteins remains incomplete due to prior focus on cis‐protein quantitativ...
Background
Blood‐based biomarkers of Alzheimer’s disease (AD) may provide an avenue for early identification of individuals at risk for AD dementia, which is a crucial task for implementing upcoming disease‐modifying therapies in clinical practice. Among blood‐based biomarkers, P‐tau217 has shown a particular sensitivity to amyloid pathology and ut...
Background
Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). Here, we pursued the largest CSF study to...
Background
in the clinical course of Alzheimer’s disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p‐tau‐mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neu...
Background
Sex and age are major risk factors for several chronic diseases. Recent human and mouse studies of age‐related molecular changes in blood provided new insights into age‐related disease biology. Cerebrospinal fluid (CSF) is more closely related to brain than blood and can provide additional insights to sex and age‐related brain diseases....
Background
Although the pivotal role of apolipoprotein E () in AD has been recognized for three decades, its function in different brain cells is far from understood. Knockout studies of the APOE gene may shed light of the function of ApoE. The aim of the present study was to unravel its function in induced pluripotent stem cell (iPSC) derived micr...
Background
Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.
Method
We performed a GWAS on sporadic Alzheimer’s disease (AD) including 540 patients and 852 controls from Argentina and Chile. We explored the variants associated with AD in Eur...
Background
Hippocampal sclerosis of aging (HS) is one of the most predominant causes of dementia in elder populations and it is often misdiagnosed as Alzheimer’s disease (AD). HS has recently been found to show a hippocampal atrophy pattern that might be key for the differentiation of this pathology from AD in the early stages of dementia.
Method...
Background
Optical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of mac...
Background
The Alzheimer Association has recently remarked the diagnostic and prognostic revolution that plasma biomarkers will mean for AD diagnosis, and highlighting the need of further research to translate them as a realistic option in the clinical practice. However, many studies to date have assessed them in research cohorts. Here we evaluated...
Background
Alzheimer’s disease (AD) is a complex disease conditioned by environmental and genetic factors. Over the last few years, Genome‐Wide Association Studies (GWAS) have gained increasing interest representing the basis of a personalized medicine that aims to facilitate interventions at the preclinical stages. In most studies, the integration...
Background
Apolipoprotein E is the major apolipoprotein found in plasma, involved in lipid transport and metabolism. Carrying the ε4 allele of the APOE gene (ApoE4) is a risk factor for developing Alzheimer’s disease (AD) and is associated with altered plasma lipid levels and lipoprotein particle distribution. The AMBAR phase 2b/3 trial is a therap...
The current demand for early intervention, prevention, and treatment of late onset Alzheimer’s disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older...
INTRODUCTION
Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.
METHODS
We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the Europ...
Changes in Amyloid-β (A), hyperphosphorylated Tau (T) in brain and cerebrospinal fluid (CSF) precedes AD symptoms, making CSF proteome a potential avenue to understand the pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identifie...
The current demand for early intervention, prevention, and treatment of late onset Alzheimer's disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older...
INTRODUCTION
The APOE gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (LOAD). However, the gene regulatory mechanisms at this locus have not been fully characterized.
METHODS
To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with RNA-seq, DNA methylation, and ChIP-seq dat...