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A common feature of these disorders is the misfolding and aggregation of \u03b1\u2010synuclein (\u03b1\u2010syn) and amyloid\u2010\u03b2 (A\u03b2) proteins into amyloid structures, which disrupt cellular homoeostasis and drive disease progression. While A\u03b2 typically forms extracellular deposits and \u03b1\u2010syn accumulates in intracellular inclusions, both ultimately contribute to neuronal damage and neurodegeneration. Increasing in vitro evidence suggests that these proteins can interact, altering their structural properties and, in turn, their biological effects; however, the consequences of their co\u2010occurrence in vivo remain unclear. To address this gap, we examined whether \u03b1\u2010syn modulates A\u03b2 deposition and associated neuroinflammation at early stages using a physiologically relevant bigenic mouse model coexpressing human \u03b1\u2010syn and APP knock\u2010in A\u03b2. Using combined histological and biochemical analysis, we characterised A\u03b2 load and microglial responses at early time points. Our results indicate that \u03b1\u2010syn expression is associated with altered early A\u03b2 deposition and microglial morphology in vivo. Specifically, while early A\u03b2 deposits were detected in both A\u03b2\/\u03b1\u2010syn and A\u03b2\u2010control mice from 2\u2009months of age, at 4 and 6\u2009months, reduced number and size of A\u03b2 microdeposits was observed in the A\u03b2\/\u03b1\u2010syn model. The reduction in A\u03b2 load was accompanied by a more ramified microglial morphology consistent with a less activated microglial state. Whether this delayed response reflects protection or impaired immune surveillance remains unclear. Our findings highlight the complexity of indirect A\u03b2 and \u03b1\u2010syn interactions and the need for further studies to clarify their functional impact. The newly generated bigenic mice provide a relevant platform to investigate early co\u2010pathology and its role in disease progression.<\/jats:p>","DOI":"10.1155\/padi\/7303965","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:55:32Z","timestamp":1780667732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Amyloid Formation and Neuroinflammatory Response in a Bigenic Mouse Model Expressing Human \u03b1\u2010Synuclein and 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