title: Multielectrode array analysis of cerebrospinal fluid in Alzheimer's disease versus mild cognitive impairment: a potential diagnostic and treatment biomarker.
abstract: Pathological cerebrospinal fluid (CSF) alterations like changes in amyloid-β1-42 and tau protein concentration are typical in Alzheimer's disease (AD). However, it remains unclear, if the composition of known or unknown pathological factors in native CSF has a functional significance in AD. In this pilot study, we used multielectrode array (MEA) neurochips to determine whether CSF of individuals with AD (AD-CSF) may have distinct neurofunctional properties that may distinguish it from that of individuals with mild cognitive impairment (MCI) - a differential diagnosis of high clinical importance. MEAs are neuronal cultures coupled to a multisite electrical recording system with the ability to reflect pharmacological or toxicological alterations on the functional level of whole neuronal networks. Collective rhythmical electrical activity was substantially enhanced after exposure to CSF of cognitively healthy subjects (controls) and of MCI individuals (MCI-CSF) alike. However, this activity increment was significantly reduced when MEAs were exposed to AD-CSF compared to MCI-CSF. Moreover, following AD-CSF exposure, networks showed significantly enhanced burst durations and less synchronous bursting, respectively. Thus, AD-CSF and MCI-CSF could be distinguished by characteristic changes of the network firing pattern on MEAs. When data of MCI individuals and AD patients were pooled, the network suppression correlated significantly with the degree of cognitive decline. The findings of this pilot study may set the stage for a unique and straightforward diagnostic bioassay of AD with particular value in the differential diagnosis to MCI and as a much needed biomarker for clinical trials.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Görtz
authors.forename: Mario
authors.initials: M
authors.lastname: Siebler
authors.forename: Ralf
authors.initials: R
authors.lastname: Ihl
authors.forename: Uwe
authors.initials: U
authors.lastname: Henning
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.forename: Tillmann
authors.initials: T
authors.lastname: Supprian
authors.forename: Christian
authors.initials: C
authors.lastname: Lange-Asschenfeldt
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D003470:Culture Media / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010865:Pilot Projects; D040081:Protein Array Analysis / Q000379:methods*; D051381:Rats
chemical_list: D015415:Biomarkers; D003470:Culture Media