BACKGROUND: The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid β(1-42) (Aβ42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints. METHODS: We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF Aβ42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini-Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD. RESULTS: We included 127 patients with subjective complaints (age 60 ± 10 years, 61 [48%] females, MMSE 29 ± 1). At baseline, Aβ42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). Aβ42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8-66.4). The adjusted HR associated with tau was 2.8 (0.9-9.2) and with ptau 2.6 (0.8-8.2). Combinations of biomarkers had a lower predictive value than Aβ42 alone. CONCLUSION: Low Aβ42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of Aβ42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.
BACKGROUND: The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid β(1-42) (Aβ42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints. METHODS: We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF Aβ42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini-Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD. RESULTS: We included 127 patients with subjective complaints (age 60 ± 10 years, 61 [48%] females, MMSE 29 ± 1). At baseline, Aβ42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). Aβ42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8-66.4). The adjusted HR associated with tau was 2.8 (0.9-9.2) and with ptau 2.6 (0.8-8.2). Combinations of biomarkers had a lower predictive value than Aβ42 alone. CONCLUSION: Low Aβ42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of Aβ42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.
Authors: Jon B Toledo; Henrik Zetterberg; Argonde C van Harten; Lidia Glodzik; Pablo Martinez-Lage; Luisella Bocchio-Chiavetto; Lorena Rami; Oskar Hansson; Reisa Sperling; Sebastiaan Engelborghs; Ricardo S Osorio; Hugo Vanderstichele; Manu Vandijck; Harald Hampel; Stefan Teipl; Abhay Moghekar; Marilyn Albert; William T Hu; Jose A Monge Argilés; Ana Gorostidi; Charlotte E Teunissen; Peter P De Deyn; Bradley T Hyman; Jose L Molinuevo; Giovanni B Frisoni; Gurutz Linazasoro; Mony J de Leon; Wiesje M van der Flier; Philip Scheltens; Kaj Blennow; Leslie M Shaw; John Q Trojanowski Journal: Brain Date: 2015-07-27 Impact factor: 13.501
Authors: Laura A Rabin; Colette M Smart; Paul K Crane; Rebecca E Amariglio; Lorin M Berman; Mercé Boada; Rachel F Buckley; Gaël Chételat; Bruno Dubois; Kathryn A Ellis; Katherine A Gifford; Angela L Jefferson; Frank Jessen; Mindy J Katz; Richard B Lipton; Tobias Luck; Paul Maruff; Michelle M Mielke; José Luis Molinuevo; Farnia Naeem; Audrey Perrotin; Ronald C Petersen; Lorena Rami; Barry Reisberg; Dorene M Rentz; Steffi G Riedel-Heller; Shannon L Risacher; Octavio Rodriguez; Perminder S Sachdev; Andrew J Saykin; Melissa J Slavin; Beth E Snitz; Reisa A Sperling; Caroline Tandetnik; Wiesje M van der Flier; Michael Wagner; Steffen Wolfsgruber; Sietske A M Sikkes Journal: J Alzheimers Dis Date: 2015-09-24 Impact factor: 4.472
Authors: Marta Cosín-Tomás; Anna Antonell; Albert Lladó; Daniel Alcolea; Juan Fortea; Mario Ezquerra; Albert Lleó; Maria José Martí; Mercè Pallàs; Raquel Sanchez-Valle; José Luís Molinuevo; Coral Sanfeliu; Perla Kaliman Journal: Mol Neurobiol Date: 2016-09-08 Impact factor: 5.590
Authors: Arno de Wilde; Wiesje M van der Flier; Wiesje Pelkmans; Femke Bouwman; Jurre Verwer; Colin Groot; Marieke M van Buchem; Marissa Zwan; Rik Ossenkoppele; Maqsood Yaqub; Marleen Kunneman; Ellen M A Smets; Frederik Barkhof; Adriaan A Lammertsma; Andrew Stephens; Erik van Lier; Geert Jan Biessels; Bart N van Berckel; Philip Scheltens Journal: JAMA Neurol Date: 2018-09-01 Impact factor: 18.302
Authors: Richard J Kryscio; Erin L Abner; Gregory E Cooper; David W Fardo; Gregory A Jicha; Peter T Nelson; Charles D Smith; Linda J Van Eldik; Lijie Wan; Frederick A Schmitt Journal: Neurology Date: 2014-09-24 Impact factor: 9.910
Authors: Nancy J Donovan; Rebecca E Amariglio; Amy S Zoller; Rebecca K Rudel; Teresa Gomez-Isla; Deborah Blacker; Bradley T Hyman; Joseph J Locascio; Keith A Johnson; Reisa A Sperling; Gad A Marshall; Dorene M Rentz Journal: Am J Geriatr Psychiatry Date: 2014-02-26 Impact factor: 4.105
Authors: Frank Jessen; Rebecca E Amariglio; Martin van Boxtel; Monique Breteler; Mathieu Ceccaldi; Gaël Chételat; Bruno Dubois; Carole Dufouil; Kathryn A Ellis; Wiesje M van der Flier; Lidia Glodzik; Argonde C van Harten; Mony J de Leon; Pauline McHugh; Michelle M Mielke; Jose Luis Molinuevo; Lisa Mosconi; Ricardo S Osorio; Audrey Perrotin; Ronald C Petersen; Laura A Rabin; Lorena Rami; Barry Reisberg; Dorene M Rentz; Perminder S Sachdev; Vincent de la Sayette; Andrew J Saykin; Philip Scheltens; Melanie B Shulman; Melissa J Slavin; Reisa A Sperling; Robert Stewart; Olga Uspenskaya; Bruno Vellas; Pieter Jelle Visser; Michael Wagner Journal: Alzheimers Dement Date: 2014-05-03 Impact factor: 21.566
Authors: R J Kryscio; E L Abner; G A Jicha; P T Nelson; C D Smith; L J Van Eldik; W Lou; D W Fardo; G E Cooper; F A Schmitt Journal: J Prev Alzheimers Dis Date: 2016-03
Authors: Rosalinde E R Slot; Sietske A M Sikkes; Johannes Berkhof; Henry Brodaty; Rachel Buckley; Enrica Cavedo; Efthimios Dardiotis; Francoise Guillo-Benarous; Harald Hampel; Nicole A Kochan; Simone Lista; Tobias Luck; Paul Maruff; José Luis Molinuevo; Johannes Kornhuber; Barry Reisberg; Steffi G Riedel-Heller; Shannon L Risacher; Susanne Roehr; Perminder S Sachdev; Nikolaos Scarmeas; Philip Scheltens; Melanie B Shulman; Andrew J Saykin; Sander C J Verfaillie; Pieter Jelle Visser; Stephanie J B Vos; Michael Wagner; Steffen Wolfsgruber; Frank Jessen; Wiesje M van der Flier Journal: Alzheimers Dement Date: 2018-12-13 Impact factor: 21.566