Nature communications · 2025
Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Meyer Carolin, Niedermeier Theresa, Feyen Paul L C, Strübing Felix L, Rauchmann Boris-Stephan, Karali Katerina, Gentz Johanna, Tillmann Yannik E, Landgraf Nicolas F, Rumpf Svenja-Lotta, Ochs Katharina, Wind-Mark Karin, Biechele Gloria, Wagner Jessica, Guersel Selim, Kurz Carolin I, Schweiger Meike, Prtvar Danilo, Shi Yuan, Banati Richard B, Liu Guo-Jun, Middleton Ryan J, Mitteregger-Kretzschmar Gerda, Perneczky Robert, Koeglsperger Thomas, Neher Jonas J, Tahirovic Sabina, Brendel Matthias, Herms Jochen, Paeger Lars
Аннотация
Alzheimer's disease (AD) often begins with non-cognitive symptoms such as olfactory deficits, which can predict later cognitive decline, though the mechanisms remain unclear. Pathologically, the brainstem locus coeruleus (LC), the main source of the neurotransmitter noradrenalin (NA) modulating olfactory information processing is affected early. Here we show early and distinct loss of noradrenergic input to the olfactory bulb (OB) coinciding with impaired olfaction in an AD mouse model, before appearance of amyloid plaques. Mechanistically, OB microglia recognize and phagocytose LC axons. Reducing phagocytosis genetically preserves LC axons and olfaction. Prodromal AD patients display elevated TSPO-PET signals in the OB, similarly to AppNL-G-F mice. We further confirm early LC axon degeneration in post-mortem OBs in patients with early AD. Our findings reveal a mechanism linking early LC damage to hyposmia in AD, suggesting olfactory testing and neurocircuit imaging for early diagnosis and enable timely therapeutic intervention for Alzheimer's disease.