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A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

Translational Neurodegeneration 2022年第1期11卷 532-546页

作者： neelam younas Leticia Camila Fernandez Flores Franziska Hopfner Günter U.Höglinger Inga Zerr Prion Research Group Department of NeurologyNational Reference Center for Surveillance of TSEUniversitätsklinikum Göttingen:Universitätsmedizin GöttingenGeorg-August UniversityGöttingenGermanyRobert-Koch-Strasse 4037075 GöttingenGermany Hannover Medical School Medizinische Hochschule HannoverHannoverGermany German Center for Neurodegenerative Diseases(DZNE) MunichGermany German Center for Neurodegenerative Diseases(DZNE) GöttingenGermany.

Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.

关键词： Alzheimer’s disease Central nervous system Diagnosis Exosomes Blood-brain barrier Parkinson’s disease

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α-Synuclein conformers reveal link to clinical heterogeneity ofα-synucleinopathies

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Translational Neurodegeneration 2023年第1期12卷 691-701页

作者： Matthias Schmitz NiccolòCandelise Sezgi Canaslan Hermann C.Altmeppen Jakob Matschke Markus Glatzel neelam younas Saima Zafar Peter Hermann Inga Zerr Department of Neurology National Reference Center for TSEThe German Center for Neurodegenerative Diseases(DZNE)Georg-August-UniversityUniversity Medicine GottingenGoettingenGermany National Center for Drug Research and Evaluation Institute Superiore di SanitàRomeItaly Institute of Neuropathology University Medical Center Hamburg-Eppendorf(UKE)HamburgGermany

α-Synucleinopathies,such as Parkinson’s disease(PD),dementia with Lewy bodies(DLB)and multiple system atrophy,are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfoldedα-synuclein(αSyn),referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions(Papp-Lantos bodies).Even though the specific cellular distribution of aggregatedαSyn differs in PD and DLB patients,both groups show a significant pathological overlap,raising the discussion of whether PD and DLB are the same or different *** clinical investigation,we will focus in addition on methodologies,such as protein seeding assays(real-time quaking-induced conversion),to discriminate between different types ofα-*** approach relies on the seeding conversion properties of misfoldedαSyn,supporting the hypothesis that different conformers of misfoldedαSyn may occur in different types ofα-*** the pathological processes influencing the disease progression and phenotype,provoked by differentαSyn conformers,will be important for a personalized medical treatment in future.

关键词： α-synucleinopathies α-synuclein RT-QuIC Protein strains

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