ArticleNature aging2026
Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.
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Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Manganese Dioxide Nanoparticles Protect PC12 Cells Against HPharmaceutics · 2026Article
- Revealing the Mechanisms of Alzheimer's, Parkinson's and Huntington's Diseases Through Invertebrate Models.Biology · 2026Review
- A Novel Nogo-A Receptor Antagonist Peptide Impedes Alzheimer's Disease Pathology by Nogo-A/NgR/ROCK Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- A combined artificial intelligence-wet lab approach identifies a pivotal role of the NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Two-photon in vivo imaging reveals cell type-specific mitophagy dynamic changes in mouse somatosensory cortex during aging.npj aging · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
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Authors and funding
40 authors.
Jun-Ping Pan *Department of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Ping-Jie Wang *Department of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Jianying Zhang *Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-8161-7536
Anne-Brita Knapskog *Department of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway.ORCID http://orcid.org/0000-0003-4867-551X
Leiv Otto Watne *Department of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway.ORCID http://orcid.org/0000-0003-0441-6700
He-Ling WangDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0002-8920-1487
Maria Jose Lagartos-DonateDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.
Sofie LautrupDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.
Li-Peng MaoDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Qian WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhi-Peng LingDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Shi-Qi ZhangDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-9751-7652
Tomás Schmauck-MedinaDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0003-4618-0628
Ruixue AiDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0001-9870-3692
Trine Holt EdwinDepartment of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway.ORCID http://orcid.org/0000-0002-0530-8771
Tianjiao ZhangCentre for Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau, China.
Ingvild SaltvedtDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Rannveig Sakshaug EldholmDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0002-5585-0446
Annabel SmithUK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-5837-6121
Kateřina VeverováMemory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-5845-1854
Domenica CaponioDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.ORCID http://orcid.org/0000-0002-3827-8943
Asgeir Kobro-FlatmoenKavli 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.
Huanhuan PangSchool of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.
Zijian WangDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Haoyun WangDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Li-Juan GaoDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Nathalie Bodd HalaasDepartment of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway.
Garry WongCentre for Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau, China.
Martin VyhnalekMemory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
Oscar Junhong LuoDepartment of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-1266-3069
William A McEwanUK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-4408-0407
Jon Storm-MathisenSynaptic 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.ORCID http://orcid.org/0000-0002-2930-3262
Li GanHelen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-4600-275X
Zeping HuSchool of Pharmaceutical Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-4146-7750
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Menno P WitterKavli 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.
Dag AarslandDepartment of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0001-6314-216X
Geir SelbækDepartment of Geriatric Medicine, Oslo University Hospital (Ullevaal), Oslo, Norway.ORCID http://orcid.org/0000-0001-6511-8219
Guobing ChenDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China. guobingchen@jnu.edu.cn.ORCID http://orcid.org/0000-0002-2401-6168
Evandro Fei FangDepartment of Microbiology and Immunology, School of Medicine; Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China. e.f.fang@medisin.uio.no.ORCID http://orcid.org/0000-0003-0355-7202
Funding
Akershus University College of Applied Science 261973Akershus University College of Applied Science 262960Akershus University College of Applied Science 263928Akershus University College of Applied Science 269901Akershus University College of Applied Science 390612Cure Alzheimer's Fund (Alzheimer's Disease Research Foundation) 282952Kreftforeningen (Norwegian Cancer Society) 207819Ministry of Health and Care Services | Helse Sør-Øst RHF (Southern and Eastern Norway Regional Health Authority) 2020001Ministry of Health and Care Services | Helse Sør-Øst RHF (Southern and Eastern Norway Regional Health Authority) 2021021Ministry of Health and Care Services | Helse Sør-Øst RHF (Southern and Eastern Norway Regional Health Authority) 2023093
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
Indexed as
AgingAlzheimer DiseaseAutophagyAutophagy-Related Protein-1 HomologIntracellular Signaling Peptides and ProteinsMitophagyAgedAged, 80 and overAnimalsCaenorhabditis elegansDisease Models, AnimalFemaleHumansMaleMiceSirtuin 1Autophagy-Related Protein-1 HomologIntracellular Signaling Peptides and ProteinsSirtuin 1tau ProteinsULK1 protein, humanUlk1 protein, mouse
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