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Alterations in certain subpopulations of synapses between neurons are thought to be a key driver of the pathological mechanisms of ALS. However, we do not have a clear understanding of which types of synapses are impacted in ALS. Identifying vulnerable synapses affected in sALS models may provide insights into the key sites of disease pathogenesis. In this study we have performed quantitative high\u2010resolution microscopy to survey different synapse subtypes, including excitatory (glutamatergic), inhibitory (glycinergic) and modulatory (cholinergic C\u2010Boutons) synapses, in the spinal cord of a mouse model of sALS showing inducible TDP\u201043 pathology (TDP43\u0394NLS) restricted to neurons. We have identified changes in cholinergic synapses and a subpopulation of excitatory synapses. Mice display robust neuronal TDP\u201043 pathology and evidence of TDP\u201043 changes at cholinergic C\u2010boutons. We also observe no evidence of astrocytic pathology nor changes in the fraction of synapses that are contacted by astrocytes. Overall, our findings highlight the selective vulnerability of distinct synapse populations in ALS.<\/jats:p>","DOI":"10.1111\/ejn.70320","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:04:58Z","timestamp":1763445898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synaptopathy in the TDP\u201043\u0394NLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis"],"prefix":"10.1111","volume":"62","author":[{"given":"Ani","family":"Ayvazian\u2010Hancock","sequence":"first","affiliation":[{"name":"School of Psychology &amp; Neuroscience University of St Andrews  St Andrews UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Psychology &amp; Neuroscience University of St Andrews  St Andrews 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