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Aging Neurosci."],"abstract":"<jats:p>Sleep disturbances are common in Alzheimer\u2019s disease (AD) and AD-related dementia (ADRD). We performed a sleep study on Tg-SwDI mice, a cerebral amyloid angiopathy (CAA) model, and age-matched wild-type (WT) control mice. The results showed that at 12 months of age, the hemizygous Tg-SwDI mice spent significantly more time in non-rapid eye movement (NREM) sleep (44.6 \u00b1 2.4% in Tg-SwDI versus 35.9 \u00b1 2.5% in WT) and had a much shorter average length of wake bout during the dark (active) phase (148.5 \u00b1 8.7 s in the Tg-SwDI versus 203.6 \u00b1 13.0 s in WT). Histological analysis revealed stark decreases of orexin immunoreactive (orexin-IR) neuron number and soma size in these Tg-SwDI mice (cell number: 2187 \u00b1 97.1 in Tg-SwDI versus 3318 \u00b1 137.9 in WT. soma size: 109.1 \u00b1 8.1 \u03bcm<jats:sup>2<\/jats:sup> in Tg-SwDI versus 160.4 \u00b1 6.6 \u03bcm<jats:sup>2<\/jats:sup> in WT), while the number and size of melanin-concentrating hormone (MCH) immunoreactive (MCH-IR) neurons remained unchanged (cell number: 4256 \u00b1 273.3 in Tg-SwDI versus 4494 \u00b1 326.8 in WT. soma size: 220.1 \u00b1 13.6 \u03bcm<jats:sup>2<\/jats:sup> in Tg-SwDI versus 202.0 \u00b1 7.8 \u03bcm<jats:sup>2<\/jats:sup> in WT). The apoptotic cell death marker cleaved caspase-3 immunoreactive (Caspase-3-IR) percentage in orexin-IR neurons was significantly higher in Tg-SwDI mice than in WT controls. This selective loss of orexin-IR neurons could be associated with the abnormal sleep phenotype in these Tg-SwDI mice. Further studies are needed to determine the cause of the selective death of orexin-IR cells and relevant effects on cognition impairments in this mouse model of microvascular amyloidosis.<\/jats:p>","DOI":"10.3389\/fnagi.2025.1529769","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T06:34:44Z","timestamp":1738650884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Yan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan R.","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031231","article-title":"Blood-brain barrier disruption increases amyloid-related pathology in TgSwDI mice.","volume":"22","author":"Abdallah","year":"2021","journal-title":"Int. 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