{
  "abstract": "Background: Sleep disturbances frequently occur in Alzheimer’s disease (AD). Although neuropeptide S (NPS) promotes wakefulness through the widely expressed NPS receptor (NPSR), its role in AD-related sleep dysregulation is unclear.\n\nAims: To investigate the effects of chronic NPS administration on AD-related sleep disturbances beyond its acute wake-promoting effects.\n\nMethods: NPSR expression was examined in the hypothalamus and hippocampus of APPswe/PS1dE9 (APP/PS1) mice, a double-transgenic mouse model of AD. Mice received intracerebroventricular NPS (1 nmol/day) for 14 days. Sleep–wake states were classified as wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Sleep architecture and amyloid-β (Aβ)-related pathology were assessed in mice. Cell-associated Aβ levels, extracellular signal-regulated kinase (ERK) phosphorylation, and autophagy-related proteins were examined in BV2 cells. Sleep responses to subsequent intracerebroventricular Aβ₁–₄₂ administration were examined in NPS-treated APP/PS1 mice.\n\nResults: APP/PS1 mice had lower NPSR protein levels in the hypothalamus and hippocampus than wild-type (WT) controls. Compared with saline-treated APP/PS1 mice, NPS-treated mice showed increased NREM sleep, reduced wakefulness, and lower Aβ-related pathology. Changes in sleep amounts were most evident during the light phase. Subsequent Aβ₁–₄₂ administration increased wakefulness and reduced NREM sleep mainly during the dark phase. It also shortened NREM episodes during the light phase. In BV2 cells, NPS altered cell-associated Aβ levels and increased ERK phosphorylation. NPS treatment was also associated with higher LC3B-II and lower p62 levels. SCH772984 attenuated the NPS-associated changes in autophagy-related proteins and cell-associated Aβ.\n\nConclusion: Chronic NPS administration improved sleep architecture and reduced Aβ-related pathology in APP/PS1 mice. The BV2 findings suggest possible involvement of ERK signaling and autophagy-related processes in cellular Aβ handling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University",
    "Jiangnan University Hospital, Jiangnan University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yiru Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Miaomiao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanjun Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Meng Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Nianshan Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyi Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangming Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongxu Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangpan Kong"
    },
    {
      "affs": [
        0
      ],
      "name": "Peng Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d82rkecssm36t.bib",
  "cited_by": 0,
  "doi": "10.3389/fneur.2026.1825666",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1825666/full",
  "id": "d82rkecssm36t",
  "issns": [
    "1664-2295"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1825666/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC346-429"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223700204",
  "pdf_url": "https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1825666/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d82rkecssm36t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:16Z",
      "native_id": "10.3389/fneur.2026.1825666",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1825666/full"
    },
    {
      "first_seen": "2026-10-30T13:47:31Z",
      "native_id": "8a3524c76e9c43b0a839feb77bdeb796",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fneur.2026.1825666"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Chronic neuropeptide S treatment improves sleep architecture and reduces Aβ-related pathology in APP/PS1 mice",
  "title_text": "Chronic neuropeptide S treatment improves sleep architecture and reduces Aβ-related pathology in APP/PS1 mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:31Z",
  "url": "https://research.draconitic.com/paper/d82rkecssm36t",
  "venue": "Frontiers in Neurology",
  "versions": []
}