{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:33:06Z","timestamp":1784241186618,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005224","name":"German Center for Neurodegenerative Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"DZNE","doi-asserted-by":"crossref","award":["BN012"],"award-info":[{"award-number":["BN012"]}],"id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["785907 (HBP SGA2)"],"award-info":[{"award-number":["785907 (HBP SGA2)"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["945539 (HBP SGA3)"],"award-info":[{"award-number":["945539 (HBP SGA3)"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["425899996 \u2013 SFB 1436"],"award-info":[{"award-number":["425899996 \u2013 SFB 1436"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated whether the impact of tau-pathology on memory performance and on hippocampal\/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A\u2212) of amyloid pathology was defined by CSF amyloid-\u03b242 (A\u03b242) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal\/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A\u2212 individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with A\u03b242 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (&amp;gt;700 pg\/ml) and phospho-tau (&amp;gt;100 pg\/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and A\u03b242 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A\u2212 groups. After classifying this matched sample for phospho-tau pathology (T\u2212\/T+), individuals with A+\/T+ were significantly more memory-impaired than A\u2212\/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer\u2019s disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer\u2019s disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function.<\/jats:p>","DOI":"10.1093\/brain\/awab405","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T19:11:18Z","timestamp":1634843478000},"page":"1473-1485","source":"Crossref","is-referenced-by-count":38,"title":["Amyloid pathology but not<i>APOE<\/i>\u03b54 status is permissive for tau-related hippocampal dysfunction"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-5388","authenticated-orcid":false,"given":"Emrah","family":"D\u00fczel","sequence":"first","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"},{"name":"Institute of Cognitive Neuroscience, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-1883","authenticated-orcid":false,"given":"David","family":"Berron","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-795X","authenticated-orcid":false,"given":"Anne","family":"Maass","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Sch\u00fctze","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Cardenas-Blanco","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzel","family":"Glanz","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"},{"name":"Clinic for Neurology, Medical Faculty, University Hospital Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coraline","family":"Metzger","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Faculty, University Hospital Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dobisch","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reuter","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Spottke","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127 Bonn, Germany"},{"name":"Department of Neurology, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Brosseron","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127 Bonn, 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T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Peters","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Berlin, 10117 Berlin, Germany"},{"name":"Clinic for Psychiatry and Psychotherapy, Charit\u00e9, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Priller","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), Berlin, 10117 Berlin, Germany"},{"name":"Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike 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