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To elucidate the relationship between the aberrant folding and aggregation of A\u03b2 and mutant Tau and neuronal function, we monitored neuronal activity in C. elegans AD models across age. For that, we used a neuronal GCaMP reporter to monitor fluctuations in Ca2+ and developed microfluidic devices to immobilize nematodes to non-invasively assess neuronal activity. Our findings revealed that expression of both A\u03b2 and Tau lead to significant reductions in neuronal activity and function in young adult animals, preceding the accumulation of amyloid aggregates. Notably, A\u03b2 expression and aggregation in muscle tissue produced detrimental effects on neuronal activity comparable to those seen after expression in neurons, suggesting that proteotoxic stress in muscle can influence neuronal function. This may occur through propagation of A\u03b2 from muscle to neurons or through retrograde signaling pathways. Further, our new sub-stoichiometrically labeled Tau strains highlight the significant impact TauP301L,V337M has on neuronal activity throughout aging. These results enhance our understanding of the early functional effects of amyloid aggregation in Alzheimer's disease.<\/jats:p>","DOI":"10.1242\/dmm.052295","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T07:56:06Z","timestamp":1771833366000},"source":"Crossref","is-referenced-by-count":0,"title":["Impairment of neuronal activity occurs at the early stages of the aggregation cascade of A\u03b21-42 and mutant Tau"],"prefix":"10.1242","volume":"19","author":[{"given":"Franziska","family":"Hirsch","sequence":"first","affiliation":[{"name":"University of Bremen 1 Department of Cell Biology , , Leobener Strasse 2, 28359 Bremen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nino","family":"F. 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