{
  "abstract": "ULK1 (Atg1) initiates macroautophagy and mitophagy, which support neuronal growth and survival, yet how this pathway is disrupted in aging and Alzheimer’s disease (AD) remains unclear. Here we report reduced ULK1 in serum and cerebrospinal fluid during aging in cognitively unimpaired participants from the COGNORM study (n = 75) and in patients with AD from the NorCog Memory Clinic Cohort (n = 316). In AD mice, ULK1 overexpression stimulates autophagic flux, reduces AD pathology and delays cognitive decline alongside increased phagocytic degradation of amyloid-β, reduced tauopathy and improved mitochondrial quality. Mechanistically, ULK1 upregulation increases autophagy and PINK1-, FUNDC1- and AMBRA1-associated mitophagy; higher autophagy and mitophagy increase cellular NAD+, which in turn deacetylates acetylated-Tau174 via the NAD+–SIRT1 axis, leading to reduced tauopathy. Using in vitro tau seeding assays and a Caenorhabditis elegans tau model, we validate the efficacy of ULK1 activators in inhibiting tauopathy. We propose that age-related decline in ULK1 leads to autophagy and mitophagy impairment and increases the progression of AD and identify ULK1 as a potential therapeutic target. Autophagic activity has a protective role in Alzheimer’s disease in mice. Here the authors investigate the role of autophagy-initiating protein ULK1 and report that its overexpression stimulates autophagic flux, reduces amyloid and tau pathology and delays cognitive decline.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway",
    "Department of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China",
    "Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Guangzhou, China",
    "Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China",
    "Xiangya School of Stomatology, Central South University, Changsha, China",
    "Department of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway",
    "Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway",
    "Institute of Clinical Medicine Campus Ahus, University of Oslo, Lørenskog, Norway",
    "Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, China",
    "Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China",
    "Centre for Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau, China",
    "Department of Geriatrics, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway",
    "Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway",
    "UK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK",
    "Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic",
    "Kavli Institute for Systems Neuroscience, K.G. Jebsen Centre for Alzheimer's Disease, Centre for Algorithms in the Cortex, Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway",
    "School of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China",
    "Institute of Clinical Medicine, Campus Ullevål, University of Oslo, Oslo, Norway",
    "Synaptic Neurochemistry and Amino Acid Transporters Labs, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences (IMB) and Healthy Brain Aging Centre (SERTA), University of Oslo, Oslo, Norway",
    "The Norwegian Centre on Healthy Ageing (NO-Age) and The Norwegian National Anti-Alzheimer's Disease (NO-AD) Networks, Oslo, Norway",
    "Helen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA",
    "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden",
    "Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK",
    "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden",
    "Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China",
    "UK Dementia Research Institute at UCL, London, UK",
    "Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA",
    "Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway",
    "Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK",
    "Faculty of Medicine, University of Oslo, Oslo, Norway",
    "Norwegian National Centre for Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway",
    "Department of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China. guobingchen@jnu.edu.cn",
    "Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Guangzhou, China. guobingchen@jnu.edu.cn",
    "Zhuhai Institute of Jinan University, Jinan University, Zhuhai, China. guobingchen@jnu.edu.cn",
    "Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway. e.f.fang@medisin.uio.no",
    "Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. e.f.fang@medisin.uio.no",
    "Department of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China. e.f.fang@medisin.uio.no",
    "Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. e.f.fang@medisin.uio.no",
    "The Norwegian Centre on Healthy Ageing (NO-Age) and The Norwegian National Anti-Alzheimer's Disease (NO-AD) Networks, Oslo, Norway. e.f.fang@medisin.uio.no"
  ],
  "article_type": null,
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  "author_total": 40,
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      "name": "Zhi‐Peng Ling"
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      "name": "Trine Holt Edwin",
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      "name": "Tianjiao Zhang"
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      "name": "Ingvild Tina Saltvedt",
      "orcid": "0000-0002-7897-9808"
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      "name": "Rannveig Sakshaug Eldholm",
      "orcid": "0000-0002-5585-0446"
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      "name": "Annabel Smith",
      "orcid": "0000-0001-5837-6121"
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      "name": "Kateřina Veverová",
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      "name": "Domenica Caponio",
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      "name": "Asgeir Kobro‐Flatmoen",
      "orcid": "0000-0002-2379-2982"
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      "affs": [
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      "name": "庞欢欢"
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      "name": "Zijian Wang"
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      "name": "Haoyun Wang"
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      "name": "Nathalie Bodd Halaas",
      "orcid": "0000-0002-6048-6423"
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      "name": "Garry Wong",
      "orcid": "0000-0003-4566-9958"
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      "name": "Martin Vyhnálek",
      "orcid": "0000-0002-5976-4932"
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      "name": "Oscar Junhong Luo",
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      "name": "William A. McEwan",
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      "name": "Jon Storm‐Mathisen",
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      "name": "Li Gan",
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      "name": "Zeping Hu",
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      "name": "Guobing Chen",
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      "name": "Evandro Fei Fang",
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  "bibtex": "https://research.draconitic.com/paper/ec1t9wz9ey9xd.bib",
  "cited_by": 19,
  "doi": "10.1038/s43587-026-01108-z",
  "fulltext_url": null,
  "id": "ec1t9wz9ey9xd",
  "issns": [
    "2662-8465"
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  "landing_url": "https://doi.org/10.1038/s43587-026-01108-z",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
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  "native_subjects": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
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      "2804|Alzheimer's disease research and treatments"
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  "pmcid": "PMC13190337",
  "pmid": "42135576",
  "published": "2026-05-14",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/ec1t9wz9ey9xd.ris",
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    {
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      "url": "https://doi.org/10.1038/s43587-026-01108-z"
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  "subjects": [
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      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
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      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
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  ],
  "title": "Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology",
  "title_text": "Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:12Z",
  "url": "https://research.draconitic.com/paper/ec1t9wz9ey9xd",
  "venue": "Nature Aging",
  "versions": []
}