{"entity": "researcher", "timestamp": "2026-08-11T15:15:23.633Z", "family": "Tjernberg", "given": "Lars O", "initials": "LO", "orcid": "0000-0001-6889-4950", "affiliations": ["Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden. lars.tjernberg@ki.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/35d7bd25361f4e08a7223926311b399a.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/35d7bd25361f4e08a7223926311b399a"}}, "publications": [{"entity": "publication", "iuid": "d89c90552d974d6ea6979a3c189833fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d89c90552d974d6ea6979a3c189833fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d89c90552d974d6ea6979a3c189833fe"}}, "title": "Intraneuronal A\u03b2 accumulation causes tau hyperphosphorylation via endolysosomal leakage.", "authors": [{"family": "Gao", "given": "Yang", "initials": "Y", "orcid": "0000-0002-7733-5365", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3c1d375765a41e0b0a7d2c0af9cb4ff.json"}}, {"family": "Wang", "given": "Lisha", "initials": "L"}, {"family": "Doeswijk", "given": "Tosca", "initials": "T"}, {"family": "Winblad", "given": "Bengt", "initials": "B"}, {"family": "Schedin-Weiss", "given": "Sophia", "initials": "S"}, {"family": "Tjernberg", "given": "Lars O", "initials": "LO", "orcid": "0000-0001-6889-4950", "researcher": {"href": "https://publications.scilifelab.se/researcher/35d7bd25361f4e08a7223926311b399a.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Alzheimers Dement", "issn": "1552-5279", "volume": "21", "issue": "3", "pages": "e70091", "issn-l": null}, "abstract": "Alzheimer's disease (AD) is characterized by amyloid beta (A\u03b2) peptide plaques and intracellular neurofibrillary tangles formed by hyperphosphorylated tau. Many attempts have been made to clarify the link between A\u03b2 and tau in the pathogenesis, but conclusive data describing a pathway for this connection are still lacking.\n\nWe developed a neuronal model of A\u03b2-induced toxicity and studied downstream effects of intraneuronal A\u03b242 accumulation on tau hyperphosphorylation using confocal microscopy and live cell imaging.\n\nA\u03b242 added to the medium was endocytosed into neurons, inducing the formation of endolysosomal protofibrils and endolysosomal leakage, which in turn promoted tau hyperphosphorylation. Asparaginyl endopeptidase (AEP) was released from the disrupted lysosomes, and inhibition of this peptidase activity reduced tau hyperphosphorylation.\n\nThe data suggest a mechanism of AD in which A\u03b242 accumulates and aggregates gradually in neurons over time, leading to endolysosomal leakage and release of AEP, which subsequently triggers tau hyperphosphorylation.\n\nA\u03b242 endocytosis leads to its endolysosomal accumulation in neurons over time. A\u03b242 polymerizes into protofibrils and causes endolysosomal leakage. Tau hyperphosphorylation is induced by endolysosomal asparagine endopeptidase leakage. Tau hyperphosphorylation is inhibited by an asparagine endopeptidase inhibitor.", "doi": "10.1002/alz.70091", "pmid": "40145397", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11947758"}], "notes": [], "created": "2026-06-11T12:35:12.376Z", "modified": "2026-06-11T12:35:30.496Z"}, {"entity": "publication", "iuid": "1d95029adc794903bf11503ddeab9127", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d95029adc794903bf11503ddeab9127.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d95029adc794903bf11503ddeab9127"}}, "title": "Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.", "authors": [{"family": "Haytural", "given": "Hazal", "initials": "H", "orcid": "0000-0002-6805-6989", "researcher": {"href": "https://publications.scilifelab.se/researcher/863ccd2db6794dff8e36a313075e4ea2.json"}}, {"family": "Benfeitas", "given": "Rui", "initials": "R"}, {"family": "Schedin-Weiss", "given": "Sophia", "initials": "S"}, {"family": "Bereczki", "given": "Erika", "initials": "E"}, {"family": "Rezeli", "given": "Melinda", "initials": "M"}, {"family": "Unwin", "given": "Richard D", "initials": "RD"}, {"family": "Wang", "given": "Xusheng", "initials": "X"}, {"family": "Dammer", "given": "Eric B", "initials": "EB", "orcid": "0000-0003-2947-7606", "researcher": {"href": "https://publications.scilifelab.se/researcher/026547f280c8451586bf92ab028090f7.json"}}, {"family": "Johnson", "given": "Erik C B", "initials": "ECB"}, {"family": "Seyfried", "given": "Nicholas T", "initials": "NT", "orcid": "0000-0002-4507-624X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c940f8678724c38b1c6e98ea1b335e4.json"}}, {"family": "Winblad", "given": "Bengt", "initials": "B", "orcid": "0000-0002-0011-1179", "researcher": {"href": "https://publications.scilifelab.se/researcher/73185a13ca474153b66415e6a2dfff0f.json"}}, {"family": "Tijms", "given": "Betty M", "initials": "BM", "orcid": "0000-0002-2612-1797", "researcher": {"href": "https://publications.scilifelab.se/researcher/74734f1c78e840b0aaadd74cc2c1ae9f.json"}}, {"family": "Visser", "given": "Pieter Jelle", "initials": "PJ"}, {"family": "Frykman", "given": "Susanne", "initials": "S"}, {"family": "Tjernberg", "given": "Lars O", "initials": "LO", "orcid": "0000-0001-6889-4950", "researcher": {"href": "https://publications.scilifelab.se/researcher/35d7bd25361f4e08a7223926311b399a.json"}}], "type": "journal article", "published": "2021-12-03", "journal": {"title": "Sci Data", "issn": "2052-4463", "volume": "8", "issue": "1", "pages": "312", "issn-l": "2052-4463"}, "abstract": "Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.", "doi": "10.1038/s41597-021-01090-8", "pmid": "34862388", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41597-021-01090-8"}, {"db": "pmc", "key": "PMC8642431"}], "notes": [], "created": "2021-12-06T08:17:14.664Z", "modified": "2024-01-16T13:48:38.002Z"}, {"entity": "publication", "iuid": "f262bf6310d1438b9abbf94866a09252", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f262bf6310d1438b9abbf94866a09252.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f262bf6310d1438b9abbf94866a09252"}}, "title": "Engineered Human Induced Pluripotent Cells Enable Genetic Code Expansion in Brain Organoids.", "authors": [{"family": "van Husen", "given": "Lea S", "initials": "LS", "orcid": "0000-0002-6737-3835", "researcher": {"href": "https://publications.scilifelab.se/researcher/381bac34b83f47bdb09fa6b78914cc5c.json"}}, {"family": "Katsori", "given": "Anna-Maria", "initials": "A", "orcid": "0000-0002-5975-2931", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a338e7f888b4e7fa663fdd87d667713.json"}}, {"family": "Meineke", "given": "Birthe", "initials": "B"}, {"family": "Tjernberg", "given": "Lars O", "initials": "LO", "orcid": "0000-0001-6889-4950", "researcher": {"href": "https://publications.scilifelab.se/researcher/35d7bd25361f4e08a7223926311b399a.json"}}, {"family": "Schedin-Weiss", "given": "Sophia", "initials": "S"}, {"family": "Els\u00e4sser", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-8724-4849", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcf26e35e037499aa1441a7738ba61af.json"}}], "type": "journal article", "published": "2021-11-16", "journal": {"title": "ChemBioChem", "issn": "1439-7633", "issn-l": "1439-4227", "volume": "22", "issue": "22", "pages": "3208-3213"}, "abstract": "Human induced pluripotent stem cell (hiPSC) technology has revolutionized studies on human biology. A wide range of cell types and tissue models can be derived from hiPSCs to study complex human diseases. Here, we use PiggyBac-mediated transgenesis to engineer hiPSCs with an expanded genetic code. We demonstrate that genomic integration of expression cassettes for a pyrrolysyl-tRNA synthetase (PylRS), pyrrolysyl-tRNA (PylT) and the target protein of interest enables site-specific incorporation of a non-canonical amino acid (ncAA) in response to an amber stop codon. Neural stem cells, neurons and brain organoids derived from the engineered hiPSCs continue to express the amber suppression machinery and produce ncAA-bearing reporter. The incorporated ncAA can serve as a minimal bioorthogonal handle for further modifications by labeling with fluorescent dyes. Site-directed ncAA mutagenesis will open a wide range of applications to probe and manipulate proteins in brain organoids and other hiPSC-derived cell types and complex tissue models.", "doi": "10.1002/cbic.202100399", "pmid": "34431592", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2021-11-17T13:17:12.910Z", "modified": "2023-06-19T11:42:30.795Z"}]}