Journal
ALZHEIMERS & DEMENTIA
Volume 11, Issue 11, Pages 1316-1328Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2014.11.008
Keywords
Alzheimer's disease; Nerve growth factor; Choline acetyltransferase; Acetyl cholinesterase; tau; Amyloid-beta; Nicotine receptors; PET; MRI
Categories
Funding
- Stockholm County Council [05817]
- Karolinska Institute [05817]
- Strategic Research Program in Neuroscience at Karolinska Institutet [05817]
- Swedish Research Council [05817]
- Swedish Alzheimer Foundation
- Gustaf V and Queen Victorias Freemason foundation
- Swedish Brain Power Consortium
- Loo & Hans Osterman Foundation
- KI Foundations
- Olle Engkvist Byggmastare Foundation
- Ake Wibergs Foundation
- Ahlen-Foundation (Ahlen-stiftelsen)
- Gunvor and Josef Aners Foundation
- Magnus Bergvalls Foundation
- Demens Foundation (Demensfonden)
- Gun and Bertil Stohnes Foundation
- Ragnhild & Einar Lundstroms Foundation
- Foundation for Sigurd & Elsa Goljes Memory
- Odd Fellow Foundation
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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. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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