Wiley, Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 11(11), p. 1316-1328, 2015
DOI: 10.1016/j.jalz.2014.11.008
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Background: Extensive loss of central cholinergic functions in 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).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. Hypothesis: EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT and acetylcholinesteraseResult: Activities of both enzymes were altered after 12 months. In particular, activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-β, in vivo cerebral glucose utilization and nicotinic binding sites, as well as morphometric and volumetric MRI measures.Conclusion: A clear pattern of associations is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy