Veranstaltung
Damage to your brain’s electrical isolation: A new risk factor for Alzheimer’s disease?| Titel der Veranstaltung | Damage to your brain’s electrical isolation: A new risk factor for Alzheimer’s disease? |
| Reihe | campus seminar |
| Veranstalter | Max-Planck-Institute für Multidisziplinäre Naturwissenschaften und für Dynamik und Selbstorganisation |
| Referent/in | Constanze Depp |
| Einrichtung Referent/in | Department of Neurogenetics |
| Veranstaltungsart | Seminar |
| Kategorie | Forschung |
| Anmeldung erforderlich | Nein |
| Beschreibung | The greatest risk factor for developing Alzheimer’s disease (AD), the leading cause of dementia, is age. But why exactly ageing constitutes the main risk factor for this disease is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of the myelin sheaths they produce. Myelin is both electrical insulation to axons and source of trophic support and, therefore, pivotal for neuronal health. We hypothesised that ageing-associated loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the primary neuropathological hallmark of AD. Here, we show that in AD mouse models different genetically induced defects of myelin or demyelinating injuries are indeed potent drivers of amyloid deposition in vivo as quantified by whole brain light sheet microscopy. Conversely, complete lack of myelin in the forebrain provides protection against plaque deposition. Mechanistically, we find that myelin dysfunction causes the accumulation of the Aβ producing machinery within axonal swellings and increases cortical amyloid precursor protein (APP) cleavage and production of Aβ. Surprisingly, AD mice with dysfunctional myelin lack plaque-corralling microglia but show a disease-associated microglia (DAM)-like signature as revealed by bulk and single cell transcriptomics. These activated microglia, however, are primarily engaged with myelin, preventing the protective reactions of microglia to Aβ plaques. Our data suggest a working model, in which age-dependent structural defects of myelin promote plaque formation, directly and indirectly, and are thus an upstream AD risk factor. Improving oligodendrocyte health and myelin integrity during ageing could be a promising target to delay AD. |
| Zeit | Beginn: 30.03.2022, 11:00 Uhr Ende: 30.03.2022 , 12:00 Uhr |
| Ort |
Max-Planck-Institut für Multidisziplinäre Naturwissenschaften (MPI-NAT, Faßberg-Campus) (Am Faßberg 11) Online |
| Kontakt |
Stefan Glöggler stefan.gloeggler@mpibpc.mpg.de |