Manuel Menéndez González

Manuel Menéndez González
University of Oviedo | UNIOVI · Department of Medicine

MD, PhD
Professor of Neurology at Departamento de Medicina, Universidad de Oviedo. Neurologist at Servicio de Neurología, HUCA.

About

200
Publications
47,265
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,974
Citations
Introduction
I am a neurologist and translational neuroscientist interested in neurodegenerative diseases. I am particularly interested in understanding the molecular mechanisms of neurodegeneration: genes, proteins and the molecular dynamics between cells, the interstitial fluid and the cerebrospinal fluid (CSF). I am also interested in developing new systems for targeted CSF drug delivery.
Additional affiliations
September 2019 - present
University of Oviedo
Position
  • Professor (Assistant)
January 2016 - present
Hospital Universitario Central de Asturias
Position
  • Neurologist
November 2010 - August 2019
University of Oviedo
Position
  • Professor (Assistant)

Publications

Publications (200)
Article
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 ris...
Article
Full-text available
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...
Article
Background Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients. Objective The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to d...
Article
Full-text available
Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease....
Article
Full-text available
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...
Article
Full-text available
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study res...
Article
Full-text available
Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis...
Article
Full-text available
Abstract Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS...
Article
Background: Many evidences suggest a pathological link between neurodegenerative diseases and cancer. In fact, several epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients and some PD genes are involved in cancer networks. Objective: The aim of this study is to assess the influence of sev...
Article
Full-text available
Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis...
Article
Full-text available
Parkinson’s disease (PD) is a complex disorder characterized by a wide spectrum of symptoms. Depression and anxiety are common manifestations in PD and may be determinants of health-related quality of life (HRQoL). The objective of this study is to determine the association of depression and anxiety with the dimensions of HRQoL in subjects with PD...
Article
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study res...
Article
Full-text available
Introduction We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson’s disease (PD) without dementia. Methods The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neuro...
Article
Full-text available
OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Males are on average ~ 1.5 times more likely to develop PD compared to females with European ancestry. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease e...
Article
Background: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spa...
Article
Background Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They are present in the general population but there is an increasing number of cases with Huntington-like phenotype reported. Methods We reviewed the medical records of cases in our centre w...
Article
Full-text available
Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analy...
Article
Full-text available
Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objectiv...
Article
Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. / Objecti...
Article
Recent studies have recognized similarities between the peptides involved in the neuropathology of Alzheimer’s disease and prions. The Tau protein and the Amyloid β peptide represent the theoretical pillars of Alzheimer’s disease development. It is probable that there is a shared mechanism for the transmission of these substances and the prion dise...
Article
Background: Visuospatial skills are impaired in Parkinson's disease (PD). Other related skills exist, such as spatial orientation have been poorly studied. The egocentric (based on internal cues) and allocentric frameworks (based on external cues) are used in daily spatial orientation. Depending on PD onset, the allocentric framework may have a hi...
Article
This study aimed to know the impact of executive functions on the performance of instrumental activities of daily living in Parkinson disease (PD). A cross-sectional descriptive study was conducted with 94 participants (64 PD and 30 controls). The poor inhibitory control and verbal fluency in PD could be related to their performance on instrumental...
Article
Full-text available
Objective: We sought to characterise C9orf72 expansions in relation to genetic ancestry and age at onset (AAO), and to use these parameters to discriminate the behavioural from the language variant syndrome, in a large pan-European cohort of frontotemporal lobar degeneration (FTLD) cases. Methods: We evaluated expansions frequency in the entire...
Article
Frontotemporal dementia (FTD) is a clinical, genetic and pathological heterogeneous group of neurodegenerative diseases. In this study, we investigated the role of APOƐ4, rs5848 in GRN and rs1042522 in TP53 gene as disease risk factors and/or phenotype modifiers in 440 frontotemporal dementia (FTD) patients, including 175 C9orf72 expansion carriers...
Article
Objective: The objective of this study was to analyze the relationship between motor complications and non-motor symptoms (NMS) burden in a population of Parkinson's disease (PD) and also in a subgroup of early PD patients. Methods: PD patients from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according...
Article
La ADL-X es una enfermedad peroxisomal causada por mutaciones en el gen ABCD1. Se caracteriza por la acumulación de ácidos grasos de cadenas muy largas en diversos tejidos, entre ellos, la sustancia blanca del sistema nervioso central. Se han descrito diversos fenotipos clínicos, sin clara correlación con el genotipo subyacente. Además, se han desc...
Article
Full-text available
Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regressi...
Article
Full-text available
An ancestral inversion of 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene, defines two haplotype clades in Caucasians (H1 and H2). The H1 haplotype has been linked inconsistently with AD. In a previous study, we showed that an SNP tagging this haplotype (rs1800547) was associated with AD risk in a large...
Article
Background: Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. / Methods: We did a meta-analysis of 17 dat...
Preprint
Full-text available
BACKGROUND: Disentangling the genetic constellation underlying Alzheimer's disease (AD) is important. Doing so allows us to identify biological pathways underlying AD, point towards novel drug targets and use the variants for individualised risk predictions in disease modifying or prevention trials. In the present work we report on the largest geno...
Article
We analyzed the frequency of intermediate alleles (IAs) in the ATXN1, ATXN2, and HTT genes in several neurodegenerative diseases. The study included 1126 patients with Alzheimer's disease (AD), 440 patients with frontotemporal dementia (FTD), and 610 patients with Parkinson's disease. In all cohorts, we genotyped ATXN1 and ATXN2 CAG repeats. In add...
Article
Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest PD genome-wide association study restricted to a single country. Methods: We performed a GWAS f...
Article
Full-text available
Background Identifying neuropsychiatric disorders is essential for prompt treatment to reduce morbidity. Among these disorders, anxiety and depression have been frequently associated with Parkinson disease (PD), particularly among elderly population. Objective The objective of this study is to determine the prevalence of anxiety and depression in...
Article
Full-text available
Amyloid β (Aβ) in brain parenchyma is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). Aβ is transported from the brain to the plasma via complex transport mechanisms at the blood-brain barrier (BBB). About 90–95% of plasma Aβ may be bound to albumin. Replacement of serum albumin in plasma has been proposed as a promi...
Article
C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood...
Article
OBJECTIVE: To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group. METHODS: The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three i...
Article
Full-text available
Background: Perrault syndrome is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing impairment and ovarian dysgenesis in females, whereas males have only hearing impairment. In some cases, patients present with a diversity of neurological signs. To date, mutations in six genes are known to cause P...
Article
Full-text available
Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We a...
Article
Objective: To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group. Methods: The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three...
Article
Background and objective: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim is to show the results of baseline evaluations of an ongoing global PD Project, COPPADIS-2015 (COhort of Patient's with PArkinson'...
Experiment Findings
Full-text available
We revised the clinical records of a series of cases where clinicians suspected Huntington’s disease and the number of CAG repeats in the HTT gene was found to be between 27 and 35, to collect their age at onset, signs, symptoms, and neuroimaging findings.
Preprint
Full-text available
Background: The Iberian peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country. Methods:...
Preprint
Full-text available
Background Genetics plays a major role in Alzheimer’s Disease (AD). To date, 40 genes associated with AD have been identified, although most remain undiscovered. Clinical, neuropathological and genetic variability might impact genetic discoveries and complicate dissection of the biological pathways underlying AD. Methods GR@ACE is a genome-wide st...
Article
Full-text available
Discrimination of case-control status based on gene expression differences has potential to identify novel pathways relevant to neurodegenerative diseases including Parkinson’s disease (PD). In this paper we applied two different novel algorithms to predict dysregulated pathways of gene expression across several different regions of the brain in PD...
Article
Huntington's disease (HD) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. Intermediate alleles (IAs) are in the range of 27–35 repeats and have been associated to a normal phenotype. The aim of this work was to analyze the association between intermediate huntingtin CAG-repeat alleles (...
Article
Full-text available
The term scans without evidence of dopaminergic deficit (SWEDD) can be associated with any patient diagnosed at first with Parkinson’s disease but with a negative dopamine transporter-single photon emission computed tomography (DaTSPECT), which does not confirm the presynaptic dopaminergic deficiency. Therefore, an alternative diagnosis should be s...
Article
Objectives: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson's disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging. Methods: Data were obtained from the Parkinson's Progression Marker Initiative. The sample included 59 partic...
Research
Full-text available
Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe th...
Article
Epilepsy is one of the most complex neurological disorders whose study requires a broad knowledge of neurology and neuroscience. It comprises a diverse group of neurological disorders that share the central feature of spontaneous recurrent seizures, and are often accompanied by cognitive deficits and mood disorder. This condition is one of the most...
Conference Paper
New opportunities are continuously arising with the evolution of technologies as Internet of Things (IoT), Big Data, e-Health, among others. In particular, the senior houses and the nursery homes can take great advantage of them in order to promote the well-aging of the community members. Not only their everyday life can be analyzed fetching for th...
Article
Full-text available
Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalised polyspike-wave discharges.
Article
Full-text available
The neuropathology of Alzheimer's disease (AD) is characterized by the widespread accumulation of neuritic plaques and neurofibrillary tangles composed of deposits of beta-amyloid peptide (Aβ) and abnormally phosphorylated tau protein (phospho-tau) respectively. Considerable effort has been expended to identify methods to retard the deposition of t...
Article
Full-text available
Liquorpheresis (cerebrospinal fluid filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators, or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. Continuous or intermittent cerebrospinal fluid (CSF) replacement...
Preprint
Full-text available
Liquorpheresis (CSF filtration) comprises a therapeutical approach that has beenproposed to treat several neurological conditions where antibodies, inflammatorymediators or abnormal peptides are the cause or play an important role in thepathogenesis of the disease. CSF replacement may be an alternative approach notexplored so far.Here, we review pr...
Preprint
Full-text available
Liquorpheresis (CSF filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. Continuous or intermittent CSF replacement may be an alternative approach not exp...
Article
Wearable devices have promoted the application of Human Activity Recognition to the development of techniques for the assessment or diagnosing of illnesses and seizures, among other applications. For instance, the use of tri-axial accelerometry (3DACM) to detect abnormal and sudden movements has been introduced in the epileptic seizure recognition....
Article
Human-activity recognition and seizure-detection techniques have gathered pace with the widespread availability of wearable devices. A study of the literature shows various studies for 3D accelerometer-based seizure detection that describe the selection of acceleration variables and controlled transformations, while discarding the remaining input v...
Conference Paper
Wearable devices are currently used in researches related with the detection of human activities and the anamnesis of illnesses. Recent studies focused on the detection of simulated epileptic seizures have found that Fuzzy Rule Base Classifiers (FRBC) can be learnt with Ant Colony Systems (ACS) to efficiently deal with this problem. However, the co...
Article
The pathophysiology of Alzheimer's disease (AD) is thought to involve the accumulation and deposition of amyloid β (Aβ) peptide in the form of plaques. It is well known that decreased cerebrospinal fluid (CSF) Aβ42 concentrations occur early in AD. Besides this, τ protein becomes hyperphosphorylated (P-τ), getting unstable and unable to bind the mi...
Article
The identification and the modeling of epilepsy convulsions during everyday life using wearable devices would enhance patient anamnesis and monitoring. The psychology of the epilepsy patient penalizes the use of user-driven modeling, which means that the probability of identifying convulsions is driven through generalized models. Focusing on clonic...
Conference Paper
Epilepsy is a neurological illness causing disturbances in the nervous system. In recent studies, a wearable device has been developed and a Hybrid Artificial Intelligent System has been proposed for enhancing the anamnesis in the case of new patients or patients with severe convulsions. Among the different Artificial Intelligent techniques that ha...
Article
Full-text available
This Research Topic is published to gather some of the latest science around neuropsychology and neuropsychiatry in neurodegenerative disorders.The call was launched in 2014 and 20 articles were eventually accepted and published, including papers on language and visuospatial functions, emotion, psychometry, brain morphometry, brain connectivity, di...