High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations.

Autor:	Sturchio A; Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.; Department of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institutet, Stockholm, Sweden., Dwivedi AK; Department of Molecular and Translational Medicine, Division of Biostatistics & Epidemiology, Texas Tech University Health Sciences Center, El Paso, TX, USA., Malm T; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Wood MJA; Department of Paediatrics, University of Oxford, Oxford, UK.; MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK., Cilia R; Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Parkinson and Movement Disorders Unit, Milan, Italy., Sharma JS; Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA., Hill EJ; Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA., Schneider LS; University of Southern California Keck School of Medicine, Los Angeles, CA, USA., Graff-Radford NR; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA., Mori H; Department of Clinical Neuroscience, Medical School, Osaka City University, Sutoku University, Abenoku, Osaka, Nagaoka, Japan., Nübling G; German Center for Neurodegenerative Diseases, Site Munich, Germany.; Department of Neurology, Ludwig-Maximilians University Munich, Germany., El Andaloussi S; Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden., Svenningsson P; Department of Clinical Neuroscience, Neuro Svenningsson, Karolinska Institutet, Stockholm, Sweden., Ezzat K; Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden., Espay AJ; Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2022; Vol. 90 (1), pp. 333-348.
DOI:	10.3233/JAD-220808
Abstrakt:	Background: In amyloid-positive individuals at risk for Alzheimer's disease (AD), high soluble 42-amino acid amyloid-β (Aβ42) 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 Aβ42 preserves normal cognition in amyloid-positive individuals with Alzheimer's 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 = 0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) ≥1.42 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±2.0 years. Soluble Aβ42 levels were higher among CDR non-progressors than CDR progressors. Higher Aβ42 predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19-0.67; p = 0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68-0.96; p = 0.018). CSF Aβ42 levels predicting lower risk of progression increased with higher SUVR levels. Conclusion: High CSF Aβ42 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations.
Databáze:	MEDLINE
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