Max Borsche

University of Lübeck · Institute of Neurogenetics

Although serum from patients with Parkinson’s disease contains elevated levels of numerous pro-inflammatory cytokines including IL-6, TNF, IL-1β, and IFNγ, whether inflammation contributes to or is a consequence of neuronal loss remains unknown¹. Mutations in parkin, an E3 ubiquitin ligase, and PINK1, a ubiquitin kinase, cause early onset Parkinson...

There is increasing evidence for a role of inflammation in Parkinson's disease. Recent research in murine models suggests that parkin and PINK1 deficiency leads to impaired mitophagy, which causes the release of mitochondrial DNA (mtDNA), thereby triggering inflammation. Specifically, the CGAS (cyclic GMP-AMP synthase)-STING (stimulator of interfer...

With newly rising coronavirus disease 2019 (COVID-19) cases, important data gaps remain on (i) long-term dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates in fixed cohorts (ii) identification of risk factors, and (iii) establishment of effective surveillance strategies. By polymerase chain reaction and antibod...

Estimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of t...

Deep intronic FGF14 repeat expansions have been identified as a frequent genetic cause of late-onset cerebellar ataxias, explaining up to 30% of patients. Interruptions between repeats have previously been identified to impact the penetrance in other repeat expansion disorders. Repeat interruptions within FGF14 have yet to be characterized in detai...

Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a primary monogenic cause of Parkinson’s disease (PD). However, the likelihood of developing PD with inherited LRRK2 pathogenic variants differs (a phenomenon known as “reduced penetrance”), with factors including age and geographic region, highlighting a potential role for li...

Background The network theory of mental disorders asserts the pivotal role of feedback loops in psychopathology. We investigated intra-individual dynamics and potential feedback loops in psychological networks and their association with long-term outcomes. Methods At the beginning of the COVID-19 pandemic, data from a population-based cohort (N =...

Non-pharmaceutical interventions (NPI) have been proven successful in a population-based approach to protect from SARS-CoV-2 transmission during the COVID-19 pandemic. As a consequential-effect, a reduction in the spread of all respiratory viruses has been observed, but the primary factors behind this phenomenon have yet to be identified. We conduc...

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN -PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN -PD was also assessed. Am...

Pathogenic variants in PRKN cause early‐onset Parkinson's disease (PD), while the role of alpha‐synuclein in PRKN ‐PD remains uncertain. One study performed a blood‐based alpha‐synuclein seed amplification assay (SAA) in PRKN ‐PD, not detecting seed amplification in 17 PRKN ‐PD patients. By applying a methodologically different SAA focusing on neur...

Background The newly discovered intronic repeat expansions in the genes encoding replication factor C subunit 1 ( RFC1 ) and fibroblast growth factor 14 ( FGF14 ) frequently cause late‐onset cerebellar ataxia. Objectives To investigate the presence of RFC1 and FGF14 pathogenic repeat expansions in Serbian patients with adult‐onset cerebellar ataxi...

Despite being a major component of Lewy bodies and Lewy neurites, pathogenic variants in the gene encoding alpha-Synuclein (α-Syn) are rare. To date, only four missense variants in the SNCA gene, encoding α-Syn have unequivocally been shown to be disease-causing. We here describe a Parkinson´s disease patient with early cognitive decline carrying a...

Purpose Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. Methods In the IMMUNEBRIDGE...

Depressive symptoms in Parkinson’s disease (PD) are multifactorial and are partly linked to the underlying dopaminergic deficit. However, at least a subset of PD patients may exhibit an unspecific depressive reaction to chronic illness. Here, we compared the prevalence and severity of depressive symptoms in PD patients and disease controls (DC). PD...

The COVID-19 pandemic remains a significant challenge to global health despite the application of vaccines to approximately 70% of the world's population [1]. Unresolved questions include the duration of immunity after infection and vaccination, the effectiveness of vaccines against new virus variants, the relationship between antibody levels and i...

Different pathogenic variants in the DNA polymerase-gamma2 (POLG2) gene cause a rare, clinically heterogeneous mitochondrial disease. We detected a novel POLG2 variant (c.1270 T > C, p.Ser424Pro) in a family with adult-onset cerebellar ataxia and progressive ophthalmoplegia. We demonstrated altered mitochondrial integrity in patients' fibroblast cu...

Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time. In the IMMUNEBRIDGE project, we harmonised d...

Background: Alterations in mito-chondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism , and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be...

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of cl...

Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner th...

Biallelic mutations in PINK1/PRKN cause recessive Parkinson’s disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA (mtDNA) integrity and inflammation as disease modifiers in carriers of mutations in these genes. MtDNA integrity was investigated in a large collection of biallelic (n...

Right from the start of the COVID pandemic in January 2020, the entire tourism sector was put under immense pressure because of its assumed role in SARS-CoV-2 transmission and infection dynamics. Based on reports of single superspreading events in the early days of the pandemic, the hotel industry appeared in a bad light that impaired a strategic r...

Zusammenfassung Hintergrund Mit dem Ausbruch der Corona-Pandemie wurde im Großraum Lübeck ab Mai 2020 die LübEcker Längsschnittuntersuchung zu Infektionen mit SARS-CoV-2 (ELISA-Studie) durchgeführt, die Aufschluss über Prävalenz, Dunkelziffer und Symptome von SARS-CoV-2-Infektionen geben sollte. Ziel der vorliegenden Arbeit ist die Bewertung defin...

Background Considering the insufficiently controlled spread of new SARS-CoV-2 variants, partially low vaccination rates, and increased risk of a post-COVID syndrome, well-functioning, targeted intervention measures at local and national levels are urgently needed to contain the SARS-CoV-2 pandemic. Surveillance concepts (cross-sectional, cohorts, c...

Biallelic mutations in PINK1 and PRKN cause recessively inherited Parkinson’s disease (PD). Though some studies suggest that PINK1 / PRKN monoallelic mutations may not contribute to risk, deep phenotyping assessment showed that PINK1 or PRKN monoallelic pathogenic variants were at a significantly higher rate in PD compared to controls. Given the es...

Background To investigate the association between disease duration and the severity of bilateral vestibulopathy in individuals with complete or incomplete CANVAS (Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome) and biallelic RFC1 repeat expansions. Methods Retrospective analysis of clinical data and the vestibulo‐ocular reflex...

Cerebral malaria is a potentially lethal disease, which is caused by excessive inflammatory responses to Plasmodium parasites. Here we use a newly developed transgenic Plasmodium berghei ANKA (PbAAma1OVA) parasite that can be used to study parasite-specific T cell responses. Our present study demonstrates that Ifnar1-/- mice, which lack type I inte...

Mutations in the Parkin (PRKN) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous PRKN mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimate...

Background Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. Objectives 1) To develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; 2) to evaluate whether presence of tremor associated with dystonia influences model pr...

Background: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibi...

Neurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cogn...

Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South...

Background More than one year into the COVID-19 pandemic, important data gaps remain on longitudinal prevalence of SARS-CoV-2 infection at the population level and in defined risk groups, efficacy of specific lockdown measures, and on (cost-)effective surveillance. Methods The ELISA (Luebeck Longitudinal Investigation of SARS-CoV-2 Infection) study...

Background Heterozygous carriers of Parkin mutations are suggested to be at risk of developing Parkinson’s disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD...

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus. there is increasing interest in metabolic and lipoprotein signatures of the disease and early analyses have demonstrated metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients....

Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson’s disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the auto...

Excessive inflammatory immune responses during infections with Plasmodium parasites are responsible for severe complications such as cerebral malaria (CM) that can be studied experimentally in mice. Dendritic cells (DC) activate cytotoxic CD8 T cells and initiate immune responses against the parasites. Batf3‐/‐ mice lack a DC subset, which efficien...

Despite a genetic component in the development of Parkinson's disease (PD), monozygotic twin pairs often display discordance for PD. Here, we describe the generation of six human induced pluripotent stem cell (iPSC) lines from dermal fibroblasts of three pairs of monozygotic twins discordant for PD. We used non-integrating Sendai virus and the iPSC...

The diagnosis of Parkinson’s disease (PD) in patients carrying mutations in the Parkin gene is frequently delayed. We confirmed this finding in a sample of nine biallelic Parkin-PD patients with a mean delay of nine years and found an inverse relationship between diagnostic delay and age at onset.

Differences in concordance rates between monozygotic and dizygotic twin pairs with Parkinson's disease (PD) have been used to estimate genetic influences in PD pathogenesis. We hypothesized that “discordance” may not in all cases adequately reflect the multifaceted disease manifestation of PD that involves a continuum from prodromal to definite PD....

Background: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD. Methods: We searche...

Zusammenfassung Monogene, also auf einem einzelnen Gendefekt beruhende Parkinson-Syndrome (PS), machen ca. 5 % aller Parkinson-Erkrankungen aus. Hierbei konnten in den letzten 20 Jahren drei autosomal-dominant ( SNCA, LRRK2, VPS35 ) und drei autosomal-rezessiv ( Parkin, PINK1, DJ-1 ) vererbte kausale Parkinson-Gene identifiziert und validiert werde...