Microchip Electrophoresis Profiling of A Peptides in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease Mohamad Reza Mohamadi, † Zuzana Svobodova, ‡ Romain Verpillot, § Hermann Esselmann, | Jens Wiltfang, | Markus Otto, ⊥ Myriam Taverna, § Zuzana Bilkova, ‡ and Jean-Louis Viovy* ,† UMR 168, Curie Institute/CNRS/Universite ´ Pierre et Marie Curie, Paris, France, Department of Biological and Biochemical Sciences, University of Pardubice, 53210 Pardubice, Czech Republic, Faculte ´ de Pharmacie, UMR 8612-LPNSS, University of Paris sud 11, Chatenay Malabry, France, Department of Psychiatry and Psychotherapy, LVR-Hospital, University of Duisburg-Essen, Virchowstrasse 174, D-45147 Essen, Germany, and Department of Neurology, University of Ulm, Steinho ¨ velstrasse 1, 89075 Ulm, Germany The preferential aggregation of A1-42 in amyloid plaques is one of the major neuropathological events in Alzhe- imer’s disease. This is accompanied by a relative reduc- tion of the concentration of A1-42 in the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer’s disease. Here, we describe a microchip gel electrophore- sis method in polydimethylsiloxane (PDMS) chip that enables rapid profiling of major A peptides in cere- brospinal fluid. To control the electroosmotic flow (EOF) in the PDMS channel and also to reduce the adsorption of the peptides to the surface of the channel, a new double coating using poly(dimethylacrylamide-co-allyl glycidyl ether) (PDMA-AGE) and methylcellulose-Tween-20 was developed. With this method, separation of five synthetic A peptides (A1-37, A1-38, A1-39, A1-40, and A1- 42) was achieved, and relative abundance of A1-42 to A1-37 could be calculated in different standard mix- tures. We applied our method for profiling of A peptides in CSF samples from nonAlzheimer patients and patients with Alzheimer’s disease. A peptides in the CSF samples were captured and concentrated using a microfluidic system in which magnetic beads coated with anti-A were self-organized into an affinity microcolumn under the a permanent magnetic field. Finally, we could detect two A peptides (A1-40 and A1-42) in the CSF samples. Neurodegenerative diseases (ND) are a major issue in human health. Alzheimer disease (AD), in particular, is one of the most common age-related neurodegenerative disorders and is becoming a paramount societal issue with the aging of the population. The reliable diagnosis of AD in the early stages has become all the more important, for several reasons. First, the disease has a very long asymptomatic evolution, probably over 10 years, during which neurological damages are, nevertheless, irreversible. Second, neuroprotective treatments able to retard the disease’s progression will hopefully be available in the future, but there is no short- term hope of treatments able to reverse the existing damages. Finally, the development of specific treatments raises the need for the differential diagnosis between different NDs. At the present time, diagnosis of AD is mainly based on clinical and neurological symptoms. At early stages, however, different forms of dementia are not easy to distinguish, and the differentiation between dementia and depression might also be difficult to obtain. Thus, there is a strong need for biomarker-supported differential diagnosis strategies for ND, able to supplement clinical and neurological ones. Although the etiology of Alzheimer’s disease (AD) is not very well-known, there is a common agreement that the accumulation of -amyloid (A) peptides in amyloid plaques is one of the hallmarks of the progression of the disease. 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