Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease. Issue 11 (9th February 2015)

• Record Type: Journal Article
• Authors: Karami, Azadeh; Eyjolfsdottir, Helga; Vijayaraghavan, Swetha; Lind, Göran; Almqvist, Per; Kadir, Ahmadul; Linderoth, Bengt; Andreasen, Niels; Blennow, Kaj; Wall, Anders; Westman, Eric; Ferreira, Daniel; Kristoffersen Wiberg, Maria; Wahlund, Lars‐Olof; Seiger, Åke; Nordberg, Agneta; Wahlberg, Lars; Darreh‐Shori, Taher; Eriksdotter, Maria
• Is Part Of: Alzheimer's & dementia. Volume 11:Issue 11(2015)
• Page Start: 1316
• Page End: 1328
• Publication Date: 2015-02-09
• Subjects: Alzheimer's disease -- Nerve growth factor -- Choline acetyltransferase -- Acetyl cholinesterase -- tau -- Amyloid‐β -- Nicotine receptors -- PET -- MRI; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2014.11.008
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: 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‐β, 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.