Biological classification; Immunity, adaptive; Immunity, innate; Neurodegenerative diseases; Neuroinflammation; Neurology; Neurology (clinical); Psychiatry and Mental Health; General Medicine
Abstract :
[en] [en] BACKGROUND: Parkinson's and Alzheimer's disease (PD/AD) are characterized by cellular pathological changes that precede clinical manifestation and symptom onset by decades (prodromal period) as well as by a heterogeneity of clinical symptoms. Both diseases are recognized as system-wide diseases with organ-transgressing dysregulation and involvement of immunological and neuroinflammatory mechanisms facilitating pathological protein aggregation and neurodegeneration.
OBJECTIVES: Overview of natural course, phenotypes and classification of PD/AD with a focus on underlying (system-wide) immunological and neuroinflammatory mechanisms.
METHODS: Literature research and consideration of expert opinions.
RESULTS: The accumulation of misfolded proteins such as amyloid‑β and synuclein in the course of neurodegenerative processes forms the basis of the current biological classifications, understanding of course and subtypes. Protein aggregation in PD/AD induces an innate immune response by activating microglia and the release of inflammatory mediators such as cytokines and chemokines and leading to further spread of neurodegeneration and accumulation of intracellular neurofibrillary tangles (NFTs). There is also growing evidence that adaptive immune responses involving auto-antibodies or auto-antigen-specific T‑/B-cell reactions involving tau, amyloid‑β or synuclein might be involved in the disease progression or subtypes of PD/AD.
CONCLUSIONS: Both innate and adaptive immune responses seem to be substantially involved in the pathological cascade leading to neurodegeneration in PD/AD and may contribute to disease progression and clinical subtypes. Thus, future targeted interventions should not only focus on protein aggregation but also on neuroinflammatory and immunological mechanisms. [de] [de] ZUSAMMENFASSUNG: HINTERGRUND: Neurodegenerative Erkrankungen wie der Morbus Parkinson und Morbus Alzheimer sind gekennzeichnet durch zelluläre Veränderungen, die der klinischen Manifestation jahrzehntelang vorausgehen können, und durch unterschiedliche Subtypen und Phänotypen der Krankheitsmanifestation. Beide Erkrankungen werden zunehmend als Systemerkrankungen verstanden, bei denen immunologische und neuroinflammatorische Mechanismen eine bedeutende Rolle spielen.
ZIEL DER ARBEIT: Übersicht über Krankheitsverlauf, Subtypen der Krankheitsmanifestation und Klassifikation im Kontext immunologischer und neuroinflammatorischer Mechanismen.
MATERIAL UND METHODEN: Literaturrecherche und Einbeziehung von Expertenmeinungen.
ERGEBNISSE: Die Akkumulation von fehlgefalteten Proteinen wie β‑Amyloid und α‑Synuklein im Rahmen des neurodegenerativen Prozesses ist aktuell Basis der biologischen Klassifikationen. In ihrer Verteilung und Ausprägung hilft sie auch für das Verständnis des Verlaufs und bei der Differenzierung einzelner Subtypen. Die Akkumulation induziert Reaktionen des angeborenen Immunsystems, die zu einer Aktivierung von Mikroglia und zur Freisetzung von Entzündungsmediatoren wie Zytokinen und Chemokinen führen. Dies kann eine weitere Ausbreitung der Neurodegeneration und eine weitere Akkumulation intrazellulärer Tau-assoziierter Neurofibrillen („tangles“) nach sich ziehen. Zunehmend gibt es Belege, das auch das adaptive Immunsystem mit einer möglichen Beteiligung von Autoantikörpern oder autoantigenspezifischen T‑Zell-Reaktionen am Krankheitsprozess beteiligt ist.
SCHLUSSFOLGERUNG: Neben Fehlfaltung, Aggregation und Akkumulation von Eiweißen im zentralen Nervensystem als Kardinalzeichen neurodegenerativer Erkrankungen spielen immunogene und neuroinflammatorische Mechanismen eine relevante Rolle. Sie könnten wichtige Ziele krankheitsmodifizierender Therapiestrategien sein.
Precision for document type :
Review article
Disciplines :
Neurology Immunology & infectious disease
Author, co-author :
Bartsch, Thorsten; Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland. t.bartsch@neurologie.uni-kiel.de ; Klinik für Neurologie, AG Gedächtnis und Plastizität, Gedächtnis- und Demenzsprechstunde, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Deutschland. t.bartsch@neurologie.uni-kiel.de
Berg, Daniela; Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Leypoldt, Frank; Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland ; Institut für Klinische Chemie, Universitätsklinikum Schleswig-Holstein, Campus Kiel und Lübeck, Kiel, Deutschland
External co-authors :
yes
Language :
German
Title :
Parkinson- und Alzheimer-Erkrankung als Systemerkrankungen.
Alternative titles :
[en] Parkinson's and Alzheimer's disease as system-wide neurodegenerative disorders.
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