title: Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease.
abstract: BACKGROUND
  The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase.
  
  
  METHODS
  Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed.
  
  
  RESULTS
  Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-β, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures.
  
  
  CONCLUSIONS
  A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Azadeh
authors: A
authors: Karami
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Helga
authors: H
authors: Eyjolfsdottir
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors: Swetha
authors: S
authors: Vijayaraghavan
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors: Göran
authors: G
authors: Lind
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors: Per
authors: P
authors: Almqvist
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors: Ahmadul
authors: A
authors: Kadir
authors: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors: Bengt
authors: B
authors: Linderoth
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Niels
authors: N
authors: Andreasen
authors: Department of Clinical Neuroscience, Clinical Neurochemistry Laboratory, University of Göteborg, Göteborg, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Nuclear medicine and PET, Department of Surgical Sciences, Uppsala University, Sweden.
authors: Anders
authors: A
authors: Wall
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Eric
authors: E
authors: Westman
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors: Daniel
authors: D
authors: Ferreira
authors: Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors: Maria
authors: M
authors: Kristoffersen Wiberg
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Lars-Olof
authors: LO
authors: Wahlund
authors: Stockholms sjukhem, Stockholm, Sweden.
authors: Åke
authors: Å
authors: Seiger
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
authors: Agneta
authors: A
authors: Nordberg
authors: NsGene Inc, Providence, RI, USA.
authors: Lars
authors: L
authors: Wahlberg
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden. Electronic address: Taher.Darreh-Shori@ki.se.
authors: Taher
authors: T
authors: Darreh-Shori
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden. Electronic address: maria.eriksdotter@ki.se.
authors: Maria
authors: M
authors: Eriksdotter
mesh_terms: D000110:Acetylcholinesterase / Q000134:cerebrospinal fluid*; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017690:Cell Transplantation; D002795:Choline O-Acetyltransferase / Q000134:cerebrospinal fluid*; D003071:Cognition / Q000502:physiology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D011877:Radionuclide Imaging; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005947:Glucose
keywords: Acetyl cholinesterase; Alzheimer's disease; Amyloid-β; Choline acetyltransferase; MRI; Nerve growth factor; Nicotine receptors; PET; tau