Pascual Sanchez-Juan

• MD, PhD
• Director at Research Foundation for Neurological Diseases

Progressive supranuclear palsy (PSP) is a rare 4-repeat tauopathy that causes behavioural, movement and cognitive abnormalities. We genotyped all available clinical and histopathological PSP cases in Spain and Portugal (N = 522), and conducted the largest PSP GWAS of the Iberian population to date. Genetic burden analysis revealed reduced diagnosti...

Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer’s disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel...

BACKROUND : Hippocampal sclerosis of aging (HS-aging) is frequently present in individuals over 85 who die with dementia. Recent studies suggest that some loci associated with Alzheimer’s disease (AD) may be more related to HS-aging. We aimed to find AD-associated SNPs potentially related to HS-aging. METHODS : We used different regression models t...

Background Plasma biomarkers for Alzheimer's disease (AD) are a promising tool for accessible and accurate biological diagnostics. However, data in clinical practice are needed to better understand their diagnostic and prognostic ability in memory unit patients. Methods We analyzed plasma phosphorylated tau at threonine 217 (p-tau217) and neurofla...

INTRODUCTION We aimed to determine whether cognitively unimpaired (CU) amyloid‐ beta‐positive (Aβ+) individuals display decreased practice effects on serial neuropsychological testing. METHODS We included 209 CU participants from three research centers, 157 Aβ− controls and 52 Aβ+ individuals. Participants underwent neuropsychological assessment a...

Background An Alzheimer's disease (AD) diagnosis made in the earliest symptomatic stages substantially benefits patients and their care partners. However, little is known regarding the clinical, healthcare system-level, and patient-specific barriers that hinder timely diagnosis and treatment. Objective To explore real-world practices surrounding t...

INTRODUCTION Hippocampal sclerosis of aging (HS-aging) is frequently present in individuals over 85 who die with dementia. Recent studies suggest that some loci associated with Alzheimer’s disease (AD) may be more related to HS-aging. We aimed to find AD-associated SNPs potentially related to HS-aging. METHODS We assessed the relation of the AD po...

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a...

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are though...

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms...

Background About 20‐30% of clinically diagnosed AD dementia patients do not meet pathologic criteria for AD and this proportion is even higher in amnestic MCI. Among tau‐negative amnestic patients, limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) has been described as a principal diagnostic alternative, especially at advanced age. LATE i...

Background Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory‐based framework, the estimation of subject...

Background In‐vivo magnetic resonance imaging (MRI) has recently shown that patients with clinically diagnosed Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) exhibit degeneration of the cholinergic nucleus basalis of Meynert and its white matter (WM) projections through the cingulum and external capsule pathways1. Here, we propose an...

Background While Lewy body (LB) pathology typically associates with a distinct clinical profile compared to Alzheimer’s disease (AD), early memory deficits are not uncommon and can confound clinical diagnosis of amnestic patients. Moreover, approximately 30‐60% of AD patients have concomitant LB pathology, which has been reported to affect the clin...

Background KLOTHO‐VS heterozygosity (KL‐VShet+) has been posited to be a protective factor against age‐related disease and cognitive decline, having been associated with increased cortical volumes and brain connectivity, as well as improved cognition in healthy elderly individuals. Conversely, the APOE‐e4 allele is a primary risk factor for the dev...

Background Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) can underlie clinical presentations mimicking Alzheimer's disease (AD). Recent imaging‐pathological studies have shown that LATE associates with a specific temporo‐limbic FDG‐PET signature that differs from the typical temporo‐parietal pattern of hypometabolism in AD and may be...

Background Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory‐based framework, the estimation of subject...

Background KLOTHO‐VS heterozygosity (KL‐VShet+) has been posited to be a protective factor against age‐related disease and cognitive decline, having been associated with increased cortical volumes and brain connectivity, as well as improved cognition in healthy elderly individuals. Conversely, the APOE‐ε4 allele is a primary risk factor for the dev...

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 To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long‐term cognitive trajectory in multi‐regional cohorts and validate the generalizability of the findings in varying clinical settings. Method Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies o...

Background Recent reports support the use of plasma biomarkers of neurodegeneration and neuroinflammation, as determined through ultrasensitive single molecular arrays (SIMOA), to screen and diagnose patients with dementia. However, their translation to clinical settings requires further studies. Methods We evaluated plasma samples from 186 indivi...

Background Limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) is a common neuropathologic finding at advanced age that associates with hippocampal sclerosis (HS) and is often comorbid with AD pathology. Neuroimaging measurements of LATE‐NC‐associated limbic degeneration have been proposed as indirect biomarkers, b...

Background Neurofilament light chain (NfL) is a fluid biomarker of axonal damage reported to be elevated in cases with dementia, and particularly in FTD. In this study we evaluate the performance of a recently developed NfL assay to be analyzed through the Lumipulse chemiluminescent platform, which is frequently available in clinical settings for t...

Background About 20‐30% of clinically diagnosed AD dementia patients do not meet pathologic criteria for AD and this proportion is even higher in amnestic MCI. Among tau‐negative amnestic patients, limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) has been described as a principal diagnostic alternative, especially at advanced age. LATE i...

Background While Lewy body (LB) pathology typically associates with a distinct clinical profile compared to Alzheimer’s disease (AD), early memory deficits are not uncommon and can confound clinical diagnosis of amnestic patients. Moreover, approximately 30‐60% of AD patients have concomitant LB pathology, which has been reported to affect the clin...

Background Neuropsychological performance guides diagnostic and therapeutic decision‐making on Alzheimer’s disease (AD) and related disorders. Despite broad recognition that amyloid‐beta (Aβ) impacts cognition during preclinical AD, the added value of Aβ‐negative norms remains uncertain. Furthermore, normative modeling is constrained by limitations...

Background In‐vivo magnetic resonance imaging (MRI) has recently shown that patients with clinically diagnosed Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) exhibit degeneration of the cholinergic nucleus basalis of Meynert and its white matter (WM) projections through the cingulum and external capsule pathways¹. Here, we propose an...

Background Practice effects are a well‐known cognitive phenomenon that is reduced in patients with Alzheimer’s disease (AD). We aimed to investigate whether cognitively unimpaired (CU) individuals within the Alzheimer’s continuum (i.e., positive amyloid‐β biomarker) display decreased practice effects on serial neuropsychological testing. Methods W...

Importance Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels. Objective To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with...

Background The advent of Alzheimer’s disease-modifying drugs requires accurate biological diagnosis to identify candidates for these therapies. So far, the most promising single plasma biomarker is phosphorylated tau at threonine 217 (p-tau217). To understand its biological features, it is essential to know its longitudinal trajectory and factors i...

Plasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological me...

Rare coding single nucleotide variants (SNV) and short insertions or deletions (indels) contribute to Alzheimer disease (AD) genetic risk, from pathogenic variants in autosomal dominant genes to risk factors with diverse effects. In contrast, copy number variants (CNV) have been scarcely studied, with the exception of a few autosomal dominant examp...

Ankle fractures can lead to issues such as limited dorsiflexion, strength deficits, swelling, stiffness, balance disorders, and functional limitations, which complicate daily activities. This study aimed to describe neuromuscular adaptations at 6 and 12 months post-surgery during static and dynamic balance tasks, specifically using the Y-Balance Te...

Importance Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. Objective To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajecto...

Background Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings i...

Background Plasma biomarkers of Alzheimer’s disease (AD), especially p-tau217, are promising tools to identify subjects with amyloid deposition in the brain, determined either by cerebrospinal fluid (CSF) or positron emission tomography. However, it is essential to measure them in an accurate and fully automated way in order to apply them in clinic...

Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array geno...

Background and Objectives Prions are misfolded prion protein assemblies that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). However, aside from the prion protein itself, molecular risk factors are not well understood. Prion and prion-like me...

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...

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...

Background Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson’s disease (PD). Objective To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2...

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer’s disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-fr...

Background Plasma biomarkers of Alzheimer’s disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective With this work we want to study the evolution of p-tau231 plasma levels i...

Background The optimal cut-off for Alzheimer’s disease (AD) CSF biomarkers remains controversial. Objective To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between ¹¹C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aβ1–42, pTau, tTau, and Aβ1–42/Aβ1–40 ratio) in our population, ca...

Background: To assess 5-year changes in regional brain metabolic patterns by ¹⁸F-FDG PET/CT in amnestic mild cognitive impairment (A-MCI) patients and link these changes to clinical outcomes and initial ¹¹C-PIB PET/CT findings. Methods: In 65 A-MCI patients diagnosed using ¹¹C-PIB and 18F-FDG PET/CT, a 5-year follow-up began. 34 patients underwent...

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 mole...

Plasma biomarkers for Alzheimer’s disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma ma...

Background Glial fibrillary acidic protein (GFAP) is a biomarker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of many neurological and neurodegenerative conditions, including AD. Recent studies have shown that its determination in blood could be especially helpful in AD diagnosis. However, the neuropathological...

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 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 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 Identifying risk factors of future conversion from cognitively normal to mild cognitive impairment is crucial for dementia prevention and understanding the clinical processes that result in the development of cognitive deterioration. One challenge which is faced with this task is that, when identifying these factors, not only the individ...

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer’s disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with risk of developing Lewy body dementia, we performed a population-based case-control study of 148,170 United States Medic...

Cantabria Cohort stems from a research and action initiative lead by researchers from Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital and University of Cantabria, supported by the regional Goverment. Its aim is to identify and follow up a cohort that would provide information to improve the understanding of the eti...

As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer’s disease is still unclear. We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineu...

Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array geno...

Background The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary...

Background There are few updated studies on the prevalence and management of Alzheimer’s disease (AD), which could be underdiagnosed or undertreated. The COVID-19 pandemic may have worsened the deficiencies in the diagnosis and treatment of these patients. Electronic medical records (EMR) offer an opportunity to assess the impact and management of...

BACKGROUND: Plasma biomarkers indicative of Alzheimer's disease pathology constitute a non-invasive tool for diagnosing and classifying the disease. They are altered even in preclinical stages. Nonetheless, it is necessary to better understand their properties so they can be helpful in a clinical context. METHODS: We have evaluated plasma phosphory...

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequenc...

Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects...

Recovery after ankle fracture surgery can be slow and even present functional deficits in the long term, so it is essential to monitor the rehabilitation process objectively and detect which parameters are recovered earlier or later. The aim of this study was (1) to evaluate dynamic plantar pressure and functional status in patients with bimalleola...

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in...

Despite decades of research, the mechanisms linking APOE to Alzheimer’s disease (AD) remain poorly understood. Finding additional risk variants at the APOE locus, beyond the common APOE‐ε2 and APOE‐ε4 alleles, may help elucidate how APOE is involved in the disease. Association with case‐control status was tested in a sequenced discovery sample (Sta...

Several plasma biomarkers have shown good correlation with brain amyloidosis measured by CSF biomarkers and PET, but their utility to identify subjects with Alzheimer’s disease(AD) brain pathology at the community level is not well known. Neuropsychological tests might be a more accessible alternative. Our aims were to assess the utility of plasma...

Background: Genome-wide Association Studies (GWAS) have reshaped our understanding of the genetic bases of complex diseases in general and neurodegenerative diseases in particular. Despite being a common disorder, dementia with Lewy bodies (DLB), which, together with Parkinson's disease dementia (PDD), comprise the umbrella term Lewy body dementias...

Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing d...

Microglia play an important role in the maintenance of brain homeostasis, and microglial dysfunction plays a causative role in Alzheimer disease pathogenesis. Here we focus on the signal regulatory protein SIRPβ1, a surface receptor expressed on the myeloid cells that triggers amyloidβ and cell debris phagocytosis via TYROBP. We found that a common...

A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ischemia.. Post-operatively, he demonstrated acute loss of retrograde autobiographical memory, prosop...

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event occurring exclusively in men and has been previously associated with Alzheimer's disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can...

Background: Previous studies suggest a link between CAG repeat number in the HTT gene and non-Huntington neurodegenerative diseases. Objective: The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α-synucleinopathies or their behavior as modulators of the phenotype. Methods: We ge...

Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missen...

Objective: Advances in our understanding of the Alzheimer’s disease (AD) continuum through in vivo biomarkers have highlighted the need to develop neuropsychological tests that are more sensitive to subtle cognitive changes in the preclinical stages of the disease. Recent data suggest that the assessment of memory retention over extended delays, to...

Primary Tauopathies are a group of diseases defined by the accumulation of Tau, in which the alteration of this protein is the primary driver of the neurodegenerative process. In addition to the classical syndromes (Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD)), ne...

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ϵ4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically h...

To analyze how balance and other physical capacities evolved after surgery in patients with a bimalleolar fracture and how these capacities and clinical variables (immobilization or unloading time) contribute to restoring patients’ functionality, 22 patients and 10 healthy people (HC) were assessed for static and dynamic balance (Y-Balance test, YB...

Background To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer’s disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI). Methods W...

Ankle fractures can cause significant functional impairment in the short and long term. In recent years, gait analysis using inertial sensors has gained special relevance as a reliable measurement system. This study aimed to evaluate the differences in spatiotemporal gait parameters and clinical–functional measurements in patients with bimalleolar...

Introduction There is a need for biomarkers to monitor the earliest phases of Parkinson's disease (PD), especially in premotor stages. Here, we studied whether there are early gait alterations in carriers of the G2019S mutation of LRRK2 that can be detected by means of an inertial sensor system. Methods Twenty-one idiopathic PD patients, 20 LRRK2-...

Background Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE *2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE . The APOE locus however re...

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID‐19 pandemic, the meeting was...

Background: Ankle fractures can cause significant functional impairment in the short and long term. In recent years, gait analysis using inertial sensors has gained special relevance as a reliable measurement system. Objectives: In patients with bimalleolar ankle fracture, to identify the differences between the operated and healthy ankle in the sp...

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 2...

Background: Damaging rare variants in the TREM2, SORL1 and ABCA7 genes have been associated with an increased risk of developing Alzheimer's Disease (AD) with odds ratios that were not observed since the identification of the main AD genetic risk factor, the APOE-ε4 allele. Here, we aimed to identify additional AD-associated genes by investigating...

Background: Mosaic loss of chromosome Y (mLOY) is a highly common somatic variant among men, and has been associated to higher risk in overall mortality and several types of disease, including Alzheimer's disease (Dumanski et al. 2016). In the present study, we aimed to replicate these findings in both a cross-sectional and longitudinal setup by d...

Background: It is well known that Alzheimer's disease (AD) has a strong genetic component. Even though it is a highly heritable disease, a big fraction of AD heritability remains to be elucidated. Genetic analysis of endophenotypes tightly linked to the disease might help to identify or confirm AD genetic risk factors. Methods: GWAS results Amyl...

Background: Genetic variants within the APOE locus may modulate Alzheimer′s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however rem...

Background Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of PD. We have studied by serial clinical and DaT-SPECT evaluations a cohort of asymptomatic carriers of LRRK2-G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended...

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphor...