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The CSF biomarkers amyloid-\u03b2<jats:sub>1\u201342<\/jats:sub> (A\u03b2<jats:sub>42<\/jats:sub>), P-tau and T-tau were analysed with xMAP technology. Cognitive, global, instrumental and basic activities of daily living (ADL) capacities at the start of ChEI therapy and semi-annually over 3\u2009years were evaluated.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>All patients had abnormal A\u03b2<jats:sub>42<\/jats:sub> (A+). Fifty-eight individuals (45%) exhibited normal P-tau and T-tau (A+\u2009T\u2013\u00a0(N)\u2013), 12 (9%) abnormal P-tau\/normal T-tau (A+\u2009T+\u00a0(N)\u2013), 17 (13%) normal P-tau\/abnormal T-tau (A+\u2009T\u2013\u00a0(N)+) and 42 (33%) abnormal P-tau and T-tau (A+\u2009T+\u00a0(N)+). The participants with A+\u2009T+\u00a0(N)+\u2009were younger than A+\u2009T\u2013\u00a0(N)+\u2009at the estimated onset of AD and the initiation of ChEIs. The proportion of 6-month responders to ChEI and deterioration\/year after start of treatment did not differ between the AT(N) profiles in any scales. A higher percentage of globally improved\/unchanged patients was exhibited in the A+\u2009T\u2013\u00a0(N)\u2013 group after 12, 30 and 36\u2009months of ChEI therapy but not at other assessments. In apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54-carriers, linear relationships were found between greater cognitive decline\/year and higher tau; Mini-Mental State Examination score\u00a0\u2013\u00a0T-tau (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u2009=\u2009\u2212\u20090.257, <jats:italic>p<\/jats:italic>\u2009=\u20090.014) and Alzheimer\u2019s Disease Assessment Scale\u2013cognitive subscale\u00a0\u2013\u00a0P-tau (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u2009=\u2009\u2212\u20090.242, <jats:italic>p<\/jats:italic>\u2009=\u20090.022). A correlation between faster progression in instrumental ADL (IADL) and higher T-tau was also detected (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u2009=\u2009\u2212\u20090.232, <jats:italic>p<\/jats:italic>\u2009=\u20090.028). These associations were not demonstrated in non-\u03b54-carriers.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Younger age and faster global deterioration were observed in AD patients with pathologic tau and neurodegeneration, whereas more rapid cognitive and IADL decline were related to higher P-tau or T-tau in <jats:italic>APOE<\/jats:italic> \u03b54-carriers only. The results might indicate an association between more pronounced tau pathology\/neuronal injury and the <jats:italic>APOE<\/jats:italic> \u03b54-allele leading to a worse prognosis. Our findings showed that the AT(N) biomarker profiles have limited utility to predict AD progression rates and, thus, measure change and interpreting outcomes from clinical trials of future therapies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12883-019-1591-0","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T12:02:42Z","timestamp":1578571362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Cerebro-spinal fluid biomarker levels: phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-0976","authenticated-orcid":false,"given":"Carina","family":"Wattmo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,9]]},"reference":[{"key":"1591_CR1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","volume":"9","author":"CR Jack Jr","year":"2010","unstructured":"Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. 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The SATS protocol and the present analyses of data were submitted to and approved by the Regional Ethical Review Board, Lund University, Lund, Sweden, no 2014\/658, dated 9 December 2014. Written informed consent was obtained from all patients included in the SATS. If an individual was not able to provide consent for him\/herself, consent was obtained from their closest relative.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CW has no competing interests. KB has served as a consultant or on advisory boards for Alzheon, Biogen, Eli Lilly, Fujirebio Europe, IBL International and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. OH has received research support (to the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2\u2009years, he has received consultancy\/speaker fees (paid to the institution) from Eli Lilly, Roche and Fujirebio.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10"}}