{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:39:23Z","timestamp":1787161163459,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phosphorylated Tau181 (pTau181) in CSF and recently in plasma has been associated with Alzheimer\u2019s disease. In the absence of amyloidopathy, individuals with increased total Tau levels and\/or temporal lobe atrophy experience no or only mild cognitive decline compared with biomarker-negative controls, leading to the proposal to categorize this constellation as suspected non-Alzheimer's disease pathophysiology (SNAP). We investigated whether the characteristics of SNAP also applied to individuals with increased CSF-pTau181 without amyloidopathy.<\/jats:p>\n                  <jats:p>In this long-term observational study, 285 non-demented individuals, including 76 individuals with subjective cognitive impairment and 209 individuals with mild cognitive impairment, were classified based on their CSF levels of pTau181 (T), total Tau (N), amyloid-\u03b242 (A\u03b242) and A\u03b242\/A\u03b240 ratio (A) into A+T+N\u00b1, A+T\u2013N\u00b1, A\u2013T+N\u00b1, and A\u2013T\u2013N\u2013. The longitudinal analysis included 154 subjects with a follow-up of more than 12 months who were followed to a median of 4.6 years (interquartile range = 4.3 years). We employed linear mixed models on psychometric tests and region of interest analysis of structural MRI data.<\/jats:p>\n                  <jats:p>Cognitive decline and hippocampal atrophy rate were significantly higher in A+T+N\u00b1 compared to A\u2013T+N\u00b1, whereas there was no difference between A\u2013T+N\u00b1 and A\u2013T\u2013N\u2013. Furthermore, there was no significant difference between A\u2013T+N\u00b1 and controls in dementia risk [hazard ratio 0.3, 95% confidence interval (0.1, 1.9)]. However, A\u2013T+N\u00b1 and A\u2013T\u2013N\u2013 could be distinguished based on their A\u03b242 and A\u03b240 levels. Both A\u03b240 and A\u03b242 levels were significantly increased in A\u2013T+N\u00b1 compared to controls.<\/jats:p>\n                  <jats:p>Long term follow-up of A\u2013T+N\u00b1 individuals revealed no evidence that this biomarker constellation was associated with dementia or more severe hippocampal atrophy rates compared to controls. However, because of the positive association of pTau181 with A\u03b2 in the A\u2013T+N\u00b1 group, a link to the pathophysiology of Alzheimer\u2019s disease cannot be excluded in this case. We propose to refer to these individuals in the SNAP group as \u2018pTau and A\u03b2 surge with subtle deterioration\u2019 (PASSED).<\/jats:p>\n                  <jats:p>The investigation of the circumstances of simultaneous elevation of pTau and A\u03b2 might provide a deeper insight into the process under which A\u03b2 becomes pathological.<\/jats:p>","DOI":"10.1093\/brain\/awac297","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T13:57:38Z","timestamp":1660658258000},"page":"4032-4041","source":"Crossref","is-referenced-by-count":25,"title":["Amyloid-\u03b2 levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2482-5851","authenticated-orcid":false,"given":"Timo Jan","family":"Oberstein","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Alexander","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Florvaag","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Klinikum Nuremberg , Nuremberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Siegmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Olm","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Utz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-605X","authenticated-orcid":false,"given":"Philipp","family":"Spitzer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Doerfler","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Lewczuk","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"},{"name":"Department of Neurodegeneration Diagnostics, Medical University of Bialystok, University Hospital of Bialystok , Bialystok , Poland"},{"name":"Department of Biochemical Diagnostics, University Hospital of Bialystok , Bialystok , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kornhuber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Maler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2022112205302409200_awac297-B1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the national institute on aging-Alzheimer\u2019s association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers 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