Summary The sustained proliferation of microglia is a key hallmark of Alzheimer’s disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We show that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterized by increased βgal activity, a senescence-associated transcriptional signature, and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. The prevention of early microglial proliferation hinders the development of senescence and DAM, impairing the accumulation of Aβ, as well as associated neuritic and synaptic damage. Overall, our results indicate that excessive microglial proliferation leads to the generation of senescent DAM, which contributes to early Aβ pathology in AD.

Fungal symbioses with plants are ubiquitous, ancient, and vital to both ecosystem function and plant health. However, benefits to fungal symbionts are not well explored, especially in non‐mycorrhizal fungi. The Foraging Ascomycete hypothesis proposes that some wood‐decomposing fungi may shift life‐history strategies to endophytism to bridge gaps in time and space between suitable substrates. To test this hypothesis we examine spatial relationships of Xylaria endophytic fungi in the forest canopy with Xylaria decomposer fungi on the forest floor. We sampled for fungi of the genus Xylaria using a spatially explicit sampling scheme in a remote Ecuadorian cloud forest, and concurrently carried out an extensive culture‐based sampling of fungal foliar endophytes. We found 36 species of Xylaria in our 0.5 ha plot, 31 of which were found to only occur as fruiting bodies. All five species of Xylaria found as endophytes were also found as fruiting bodies. We also tested the relationships of both stages of these fungi to environmental variables. Decomposer fungi were differentiated by species‐specific habitat preferences, with three species being found closer to water than expected by chance. In contrast, endophytes displayed no sensitivity to environmental conditions, such as host, moisture, or canopy cover. We found evidence of spatial linkage between life stages in two species. We also demonstrate that direct transmission of endophytes from leaves to woody substrates is possible. These results indicate that endophytism may represent one way for decomposer fungi to escape moisture limitation, and that endophytic fungi may act as sources of dispersal for decomposer fungi consistent with predictions of the Foraging Ascomycete hypothesis.

The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we sought to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesising that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We found that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterised by increased bgal activity, a senescence-associated transcriptional signature and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. Prevention of early microglial proliferation hindered the development of senescence and DAM, impairing the accumulation of Ab and associated neuritic damage. Overall, our results support that excessive microglial proliferation leads to the generation of senescent DAM, which contribute to early Ab pathology in AD.