Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
2015; Wiley; Volume: 11; Issue: 11 Linguagem: Inglês
10.1016/j.jalz.2014.11.008
ISSN1552-5279
AutoresAzadeh Karami, Helga Eyjolfsdottir, Swetha Vijayaraghavan, Göran Lind, Per Almqvist, Ahmadul Kadir, Bengt Linderoth, Niels Andreasen, Kaj Blennow, Anders Wall, Eric Westman, Daniel Ferreira, Maria Kristoffersen Wiberg, Lars‐Olof Wahlund, Åke Seiger, Agneta Nordberg, Lars U. Wahlberg, Taher Darreh‐Shori, Maria Eriksdotter,
Tópico(s)Cholinesterase and Neurodegenerative Diseases
ResumoAbstract 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.
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