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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, Stockholm, Sweden..
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, Stockholm, Sweden..
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden..
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2015 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 11, 1316-1328 p.Article in journal (Refereed) Published
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Abstract [en]

Introduction: 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. Method: 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-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: 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.

Place, publisher, year, edition, pages
2015. Vol. 11, no 11, 1316-1328 p.
Keyword [en]
Alzheimer's disease, Nerve growth factor, Choline acetyltransferase, Acetyl cholinesterase, tau, Amyloid-beta, Nicotine receptors, PET, MRI
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Neurosciences
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URN: urn:nbn:se:uu:diva-270455DOI: 10.1016/j.jalz.2014.11.008ISI: 000365162900006PubMedID: 25676388OAI: oai:DiVA.org:uu-270455DiVA: diva2:895645
Available from: 2016-01-19 Created: 2015-12-28 Last updated: 2017-11-30Bibliographically approved

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Wall, Anders

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