{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:05:41Z","timestamp":1790701541818,"version":"4.1.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,10,25]]},"abstract":"<jats:p>Background: In amyloid-positive individuals at risk for Alzheimer\u2019s disease (AD), high soluble 42-amino acid amyloid-\u03b2 (A\u03b242) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort. Objective: To test the hypothesis that high A\u03b242 preserves normal cognition in amyloid-positive individuals with Alzheimer\u2019s disease (AD)-causing mutations (APP, PSEN1, or PSEN2) to a greater extent than lower levels of brain amyloid, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), or total tau (t-tau). Methods: Cognitive progression was defined as any increase in Clinical Dementia Rating (CDR\u200a=\u200a0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) \u22651.42 by Pittsburgh compound-B positron emission tomography (PiB-PET). We used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity analyses, including Cox regression. Results: Of 232 mutation carriers, 108 were PiB-PET-positive at baseline, with 43 (39.8%) meeting criteria for progression after 3.3\u00b12.0 years. Soluble A\u03b242 levels were higher among CDR non-progressors than CDR progressors. Higher A\u03b242 predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19\u20130.67; p\u200a=\u200a0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68\u20130.96; p\u200a=\u200a0.018). CSF A\u03b242 levels predicting lower risk of progression increased with higher SUVR levels. Conclusion: High CSF A\u03b242 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations.<\/jats:p>","DOI":"10.3233\/jad-220808","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T13:57:33Z","timestamp":1663336653000},"page":"333-348","source":"Crossref","is-referenced-by-count":56,"title":["High Soluble Amyloid-\u03b242 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer\u2019s Disease-Causing Mutations"],"prefix":"10.1177","volume":"90","author":[{"given":"Andrea","family":"Sturchio","sequence":"first","affiliation":[{"name":"Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson\u2019s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA"},{"name":"Department of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Dominantly Inherited Alzheimer Consortia (DIAN)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok K.","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, Division of Biostatistics & Epidemiology, Texas Tech University Health Sciences Center, El Paso, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Malm","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.A.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Oxford, UK"},{"name":"MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Cilia","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Parkinson and Movement Disorders Unit, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson\u2019s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson\u2019s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lon S.","family":"Schneider","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neill R.","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Medical School, Osaka City University, Sutoku University, Abenoku, Osaka, Nagaoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"N\u00fcbling","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases, Site Munich, Germany"},{"name":"Department of Neurology, Ludwig-Maximilians University Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"El Andaloussi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Svenningsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kariem","family":"Ezzat","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"Department of Neurology, James J. and Joan A. 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