Katrin Beyer

Fundació Institut Investigació Germans Trias i Pujol · Pathology

The Monogenic Network of the Global Parkinson's Genetics Program (GP2) aims to create an efficient infrastructure to accelerate the identification of novel genetic causes of Parkinson's disease (PD) and to improve our understanding of already identified genetic causes, such as reduced penetrance and variable clinical expressivity of known disease-c...

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and toge...

Introduction: Isolated REM sleep behavior disorder (IRBD) represents an early manifestation of the synucleinopathies Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Aggregation of abnormal α-synuclein and its increased expression in the brain is crucial in the development of the synucleinopathies. Whereas α-synuclein gene (SNCA) tran...

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohort...

The use of saliva as a biomarker source has advantages over other biofluids and imaging techniques, and miRNAs are ideal biomarker candidates. They are involved in numerous cellular processes, and their altered expression suggests that miRNAs play a crucial regulatory role in disease development. We wanted to find an easily reproducible and executa...

Introduction In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Córdoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. Met...

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (...

Purpose of the review: The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathwa...

Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA1...

Lewy body disorders (LBD) include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). They are synucleinopathies with a heterogeneous clinical manifestation. As a cause of neuropathological overlap with other neurodegenerative diseases, the establishment of a correct clinical diagnosis is still challenging, and clinical management may be...

Background Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets have been previously related to neurodegeneration. T...

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (mi...

Background: Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodi...

Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the developm...

Increased life expectancy impacts directly on the number of older people worldwide with the associated increase in neurodegenerative diseases. Besides their social implications, the different forms of dementia, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies or frontotemporal dementia, show clinical and pathological ov...

Dementia with Lewy bodies (DLB) shows overlapping features with Alzheimer disease (AD) leading to its misdiagnosis and hindering its adequate treatment. It is well established that microRNAs play an important role in neurodegeneration and they can be found in brain and the central nervous system. Since 30 years ago, the presence of RNA (mRNA and mi...

Lewy body diseases (LBD) include Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and together with Alzheimer's disease (AD) they show an important neuropathological and clinical overlap. The human alpha- and beta-synuclein genes (SNCA and SNCB) are key factors for the development of Lewy body diseases. Here, we aimed to analyze the gen...

Dementia with Lewy bodies (DLB) shows overlapping features with Alzheimer disease (AD) leading to its misdiagnosis and hindering its adequate treatment. It is well established that microRNAs (miRNAs) play an important role in neurodegeneration and they can be found in brain and the central nervous system. EVs contain miRNAs and their size allows th...

Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency star...

Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disease. Despite decades of research, no disease modifying therapy is available and a change of research objectives and/or development of novel research tools may be required. Much AD research has been based on experimental models using animals with a short lifespan that hav...

Introduction: Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their...

The synuclein family is composed of three members, two of which, α- and β-synuclein, play a major role in the development of synucleinopathies, including Parkinson's disease (PD) as most important movement disorder, dementia with Lewy bodies (DLB) as the second most frequent cause of dementia after Alzheimer's disease and multiple system atrophy. W...

We present unexpected neuropathological findings in a 37 year old woman who underwent surgery for removal of an epidermoid cyst. A first brain MRI at the age of 27 years (due to hyperprolactinemia) showed a cystic lesion in the right prepontine region involving the cisterna ambiens with supratentorial extension. The lesion remained stable until she...

One of the major challenges in the EV field is to find a consensus method for EVs isolation. UC has been the most widely used method although new methodologies are emerging. Lately, a cold acetone-based protein precipitation method, PRotein Organic Solvent PRecipitation (PROSPR), has been reported. Here, we have isolated EVs from plasma samples by...

Extracellular vesicles (EVs) have become an attractive field among the scientific community. Yet, a major challenge is to define a consensus method for EVs isolation. Ultracentrifugation has been the most widely used methodology but rapid methods, including Size Exclusion Chromatography (SEC) and/or precipitating agents such as Polyethylene glycol...

Background: Alpha- and beta-synuclein genes (SNCA and SNCB) are involved in the development of synucleinopathies. Formation of Lewy pathology is the result of alpha-synuclein aggregation that may be inhibited by beta-synuclein. Aims: To analyze genotype distribution of potentially functional SNPs on SNCA and SNCB to identify a possibly differential...

Background: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by similar pathological features. Several studies have shown a relation between alterations in the glucocerebrosidase gene (GBA) and the development of LB diseases. Here, we explored the role of GBA mutations in Spanish DLB patients. Meth...

Parkinson disease (PD) and dementia with Lewy Bodies (DLB) are Lewy body disorders (LBD), characterized by Lewy bodies deposition. DLB additionally shows overlapping pathological and clinical features with Alzheimer disease making it difficult to diagnose and carry out disease-specific treatment. Moreover, about 20-50% of PD patients develop dement...

Since cystatin C (CysC) in involved in some forms of neurodegeneration, we investigated the possible relationship between CysC and multiple system atrophy (MSA), including its parkinsonian (MSAp) and cerebellar (MSAc) phenotypes. Cystatin C gene (CST3) haplotypes were determined by PCR followed by KspI digestion in 50 MSA patients and 108 controls....

"Although all patients fulfill diagnostic criteria fitting within a certain spectrum of symptoms and disease course, the primary cause of dementia with Lewy bodies may not be the same in all cases."

Mutations in the gene encoding glypican (GPC) 3 appear to be responsible for most cases of Simpson-Golabi-Behmel syndrome type 1. Duplication of the GPC4 gene has also been associated to this syndrome; however, no duplications involving GPC3 have been related. We describe a family that harbors a novel exon 2-4 duplication event leading to a truncat...

Lewy body diseases include Parkinson disease and dementia with Lewy bodies and are characterized by the widespread distribution of Lewy bodies in virtually every brain area. The main component of Lewy bodies is alpha-synuclein (AS). Accumulating evidence suggests that AS oligomerization and aggregation are strongly associated with the pathogenesis...

Patients with autosomal dominant Segawa disease (dopa-responsive dystonia) demonstrate excellent, sustained response to low-dose levodopa. In contrast, the development of levodopa limiting treatment dyskinesias is thought to support the diagnosis of other early-onset dystonia/parkinsonism syndromes. We describe an atypical phenotype of persistent t...

Lewy body diseases (LBDs) include dementia with Lewy bodies (DLB) and Parkinson disease (PD). Alpha-synuclein (AS) aggregation is a key event in the pathogenesis of LBDs and beta-synuclein (BS) inhibits AS aggregation in vitro and in vivo. Recently, BS has been shown to interact directly with AS regulating its functionality and preventing its oligo...

Parkinson disease (PD) is the most important movement disorder and about 50% of patients develop dementia over the time. PD belongs to the group of Lewy body disorders. Alpha-synuclein (AS) is the main component of Lewy bodies and its aggregation is a key event in the pathogenesis of PD. Beta-synuclein (BS) inhibits AS aggregation in vitro and in v...

Segawa disease is a rare dystonia due to autosomal dominant guanosine triphosphate cyclohydrolase I (adGTPCH) deficiency, affecting dopamine and serotonin biosynthesis. Recently, the clinical phenotype was expanded to include psychiatric manifestations, such as depression, anxiety, obsessive-compulsive disorder, and sleep disturbances. Although cog...

Lewy body diseases include dementia with Lewy bodies and Parkinson's disease. Whereas dementia with Lewy bodies and Parkinson's disease can be distinguished as separate clinical entities, the pathological picture is very often identical. alpha-synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and beta-synuclein inhibits...

Lewy body diseases include dementia with Lewy bodies and Parkinson's disease. Whereas dementia with Lewy bodies and Parkinson's disease can be distinguished as separate clinical entities, the pathological picture is very often identical. α-synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and β-synuclein inhibits α-synu...

Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency is an inborn error of neurotransmitter metabolism, with a prevalence of 0.5 per million, caused by mutations/deletions in the GCH1 gene. The finding of the mutation Q89X in the GCH1 gene in 23 patients from two pedigrees in an area inhabited by a population of 800,000 prompted us...

Primary renal cell carcinoma (RCC) is the most frequent kidney cancer. In renal transplant patients, RCC more commonly arise in the native kidneys, whereas allograft involvement has been just occasionally reported. In these latter cases, a graft origin of tumor cells should be considered and other recipients from the same donor should be investigat...

Lewy body diseases are characterized by the presence of Lewy bodies, alpha-synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pat...

Alpha-synuclein, parkin, and synphilin-1 are proteins mainly involved in the pathogenesis of Lewy body (LB) diseases. mRNAs of all three undergo alternative splicing, so that the existence of various isoforms has been described. Since increasing evidence supports the importance of differential isoform-expression changes in disease development, we h...

Alternative splicing is an important mechanism to generate a large number of mRNAs, thus increasing proteome diversity and tissue specificity. Three transcript variants of alpha-synuclein, a neuronal protein mainly involved in synapses, have been described so far. Whereas alpha-synuclein 140 is the whole and main transcript, alpha-synuclein 112 and...

Dementia with Lewy bodies (DLB), the second most frequent cause of dementia after Alzheimer disease (AD), is characterized by the widespread distribution of Lewy bodies in virtually every brain area. Clinically, DLB is distinguished from AD by fluctuating cognition, prominent visual hallucinations and parkinsonism, and from Parkinson disease, by th...

Synucleinopathies are characterized by the presence of different types of alpha-synuclein (AS)-positive inclusion in the brain. Thus, whereas Lewy bodies are the hallmark of Parkinson disease and dementia with Lewy bodies, glial and neuronal cytoplasmic inclusions are shown by multiple system atrophy. Because the main component of all these inclusi...

Alternative splicing gives rise to at least seven parkin and eight synphilin-1 isoforms. Since both parkin and synphilin-1 have been involved in Lewy body (LB) formation, we decided to explore whether their isoforms are differentially expressed in LB diseases. With this aim, we studied relative mRNA expression levels of parkin and synphilin-1 isofo...

alpha-Synuclein, the main component of proteinaceous inclusions in synucleinopathies, is centrally involved in aggregation processes preceding Lewy body formation. Here we describe a new alpha-synuclein gene poly-T polymorphism that is situated upstream to exon 3 and consists of three different alleles. A correlation between poly-T length and expre...

The aim of our work was to detect minor loci acting as Alzheimer's disease (AD) genetic markers. We divided 206 AD patients and 186 individuals as controls into six age at onset/age-dependent groups. We studied polymorphisms of the genes of apolipoprotein E (APOE) and its promoter, cathepsin D, butyrylcholinesterase, cystatin C, methionine synthase...

Alpha-synuclein aggregation is thought to be a key event in the pathogenesis of synucleinopathies. Although different alpha-synuclein alterations and modifications have been proposed to be responsible for early aggregation steps, the mechanisms underlying these events remain unclarified. Alpha-synuclein is a small protein localized to synaptic term...

Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration. Three different isoforms (alpha-synuclein 112, 126, and 140) resulting from alternative splicing have been described so far. The present study explores alpha-synuclein 126 mRNA expression levels...

Background and aim To determine the possible relationship between Val158Met genotypes of the COMT gene and the severity of fibromyalgia (FM) syndrome. Patients and methods The study included 110 patients aged between 45 and 55 years old diagnosed with FM (ACR, 1990) and 110 samples from control subjects with no pain and no abnormal fatigue (Nation...

To determine the possible relationship between Val158Met genotypes of the COMT gene and the severity of fibromyalgia (FM) syndrome. The study included 110 patients aged between 45 and 55 years old diagnosed with FM (ACR, 1990) and 110 samples from control subjects with no pain and no abnormal fatigue (National DNA Bank, Spain). To measure the sever...

We have determined Val158Met COMT polymorphism genotypes (HH or Val/Val, HL or Val/Met, LL or Met/Met) in 46 fibromyalgia syndrome (FS) patients and 40 controls. A correlation between these alleles and Interleukin-6 (IL-6) and Interleukin-10 (IL-10) expression levels, determined by real-time RT-PCR, has been established. The accumulation of Met-all...

Dementia with Lewy bodies (DLB) is characterized by the widespread presence of Lewy bodies (LBs) in the brain. alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. We compared alpha-synuclein 112 and alpha-synuclein 140 expression levels in...

Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies. It is currently unknown, however, whether any of the APP isoforms is instrumental in alpha-synuclein deposition in dementia with Lewy bodies (DLB). Using real-time RT-PCR, we have studied relative mRNA expression levels of APP isof...

One of the known risk factors for developing Alzheimer disease (AD) is hyperhomocysteinemia. The latter may result from mutations of the genes coding for three key enzymes involved in homocysteine metabolism (methylenetetrahydrofolate reductase [MTHFR], methionine synthase [MS], and cystathionine beta-synthase [CBS]). Polymorphisms within the three...

One of the known risk factors for developing Alzheimer disease (AD) is hyperhomocysteinemia. The latter may result from mutations of the genes coding for three key enzymes involved in homocysteine metabolism (methylenetetrahydrofolate reductase [MTHFR], methionine synthase [MS], and cystathionine beta-synthase [CBS]). Although MTHFR and MS polymorp...

Alzheimer disease (AD) patients show increased plasma levels of homocysteine, whose conversion to methionine is catalyzed by methionine synthase (MS). Although altered MS activity may result from the MS A2756G polymorphism, the latter's possible associ-ation with AD remains unexplored. To assess whether the MS A2756G polymorphism holds any influenc...

Several polymorphisms in the apolipoprotein E (APOE) promoter region have been recently described. Of interest, APOE gene expression is increased in association with the -491AT polymorphism T-allele and decreased in relation to the Th1/E47cs polymorphism G-allele. In the present study we have investigated both polymorphisms in a series of 183 Alzhe...

Cystatin C is an amyloidogenic protein that colocalizes with beta-amyloid (Abeta) within arteriolar walls in Alzheimer disease (AD) brains. Recently, a coding polymorphism in the cystatin C gene (CST3) has been claimed to confer risk for the development of late-onset AD. In the present work we have tested the frequencies of CST3-A and CST3-G allele...

Mutations in the presenilin-2 (PS-2) gene are less frequent than mutations in the PS-1 gene. All mutations described in the PS-1 gene were found in early-onset Alzheimer's disease (AD) patients. At present, there are two missense mutations described for the PS-2 gene in some AD pedigrees. We have therefore analyzed transmembrane 2 (TM2) and TM5 dom...

Alzheimer’s disease (AD) is a devastating neurologic disorder that affects more than 20 million individuals of all races and ethnic backgrounds. The incidence of AD in the general population is about 1%, with a prevalence of 5–15% in people older than 65 years of age. AD is an etiologically and genetically heterogeneous disorder. So far, 4 chromoso...

Both senile dementia (SD) and hypertension (HBP) are pathologies with a high prevalence (Applegate, 1989; Cacabelos, 1995). SD is the third health problem in developed countries after cardiovascular disease and cancer (with a prevalence of 5–15 % after the age of 65 (Cacabelos, 1995). Hypertension is a risk factor classically associated with SD of...

In Familial Alzheimer’s disease (FAD), a devastating neurodegenerative process mainly characterized by loss of learning and memory, the genetic contributions are been clarified day by day. Mutations on chromosome 21 and 19 AD-related have been described and well documented in some patients and their relatives (St. George-Hyslop et al., 1987; Murrel...

Behavioral changes, mood-related disturbances and sleep disorders are the major cause of institutionalization and caregiver concern in families with Alzheimer’s disease (AD) (Rabins et al., 1982; Steele et al., 1990; Morris et al., 1996). The estimated prevalence of psychiatric symptoms in AD accounts for 40–60% of the cases (Ballard et al., 1995)....

A general methodology for the analysis of human diseases at the nucleic acid level has been described. This method consists of a semiautomated, nontoxic analytic procedure, staining DNA bands with silver nitrate instead of ethidium bromide after DNA amplification by PCR. This technique provides a sensitive assay with enhanced accuracy and offers th...

Behavioral dysfunction is a problem in patients with Alzheimer disease (AD), and is apparent in up to 67% of individuals. Such changes are a primary cause of individual institutionalization and often lead to their functional disability. As AD progresses, the worsening of behavioral dysfunction becomes increasingly evident and is linked with decreas...

Although memory disorders and the aphaso-apraxo-agnosic syndrome are the most relevant clinical symptoms in dementia, behavioral changes, mood-related disturbances and sleep disorders are the major cause of institutionalization and caregiver concern. In the present study we have investigated the frequency and progression of cognitive and noncogniti...

International guidelines recommend for the early diagnosis of Alzheimer disease (AD) to proceed according to the following steps: 1) diagnostic criteria (DSM-IV/NINCDS-ADRDA); 2) clinical evaluation (general, neurologic, psychiatric); 3) biochemical study (blood, urine); 4) neuropsychological assessment (cognitive, functional, behavioral); 5) neuro...