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Because neuronal dysfunctions are among the earliest AD-related alterations, we asked whether they are already detectable in the retina during the pre-symptomatic stage in a APPswePS1dE9 (APP\/PS1) mouse model. The age chosen for the study (3\u20134 months) corresponds to the pre-symptomatic stage because no retinal A\u03b2 was detected, in spite of the presence of \u03b2CTF (the first cleavage product of APP). We observed an increase in ERG amplitudes in APP\/PS1 mice in comparison to the controls, which indicated an increased retinal neuron activity. These functional changes coincided with an increased expression of retinal TNF\u03b1 and its receptors type-1 (TNFR1). Consistently, the IkB expression increased in APP\/PS1 mice with a greater proportion of the phosphorylated protein (P-IkB) over total IkB, pointing to the putative involvement of the NFkB pathway. Because TNF\u03b1 plays a crucial role in the control of neuronal excitability, it is likely that, as in the hippocampus, TNF\u03b1 signaling via the TNFR1\/NFkB pathway may be also involved in early, AD-associated, retinal neuron hyperexcitability. These results further demonstrate the interest of the retina for early disease detection with a potential to assess future therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells11101650","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T13:06:23Z","timestamp":1652706383000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Concomitant Retinal Alterations in Neuronal Activity and TNF\u03b1 Pathway Are Detectable during the Pre-Symptomatic Stage in a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-0253","authenticated-orcid":false,"given":"Virginie","family":"Dinet","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Universit\u00e9s, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5480-3429","authenticated-orcid":false,"given":"Louiza","family":"Arouche-Delaperche","sequence":"additional","affiliation":[{"name":"Institut de la Vision, Sorbonne Universit\u00e9, Inserm, CNRS, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"D\u00e9gardin","sequence":"additional","affiliation":[{"name":"Institut de la Vision, Sorbonne Universit\u00e9, Inserm, CNRS, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Naud","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Universit\u00e9s, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Picaud","sequence":"additional","affiliation":[{"name":"Institut de la Vision, Sorbonne Universit\u00e9, Inserm, CNRS, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slavica","family":"Krantic","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Universit\u00e9s, 75006 Paris, France"},{"name":"Inserm UMRS 938, Team \u201cImmune System and Neuroinflammation\u201d, H\u00f4pital Saint-Antoine, 184 rue du Faubourg St-Antoine, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","article-title":"A\/T\/N: An Unbiased Descriptive Classification Scheme for Alzheimer Disease Biomarkers","volume":"87","author":"Jack","year":"2016","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward Defining the Preclinical Stages of Alzheimer\u2019s Disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association Workgroups on Diagnostic Guidelines for Alzheimer\u2019s Disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The Amyloid Hypothesis of Alzheimer\u2019s Disease: Progress and Problems on the Road to Therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1146\/annurev-neuro-080317-061725","article-title":"What Happens with the Circuit in Alzheimer\u2019s Disease in Mice and Humans?","volume":"41","author":"Zott","year":"2018","journal-title":"Annu. 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