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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
Author(s) -
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 LarsOlof,
Seiger Åke,
Nordberg Agneta,
Wahlberg Lars,
DarrehShori Taher,
Eriksdotter Maria
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.11.008
Subject(s) - choline acetyltransferase , basal forebrain , cholinergic , cholinergic neuron , nerve growth factor , acetylcholinesterase , acetylcholine , medicine , endocrinology , neuroscience , cerebrospinal fluid , psychology , pathology , chemistry , biochemistry , enzyme , receptor
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.