ORIGINAL RESEARCH published: 25 April 2022 doi: 10.3389/fnagi.2022.756687 Edited by: Takako Fujioka, Stanford University, United States Reviewed by: Grace M. Clements, University of Illinois at Urbana-Champaign, United States Daniel Dautan, Italian Institute of Technology (IIT), Italy Vinay V. Parikh, Temple University, United States *Correspondence: Vesna Jelic vesna.jelic@ki.se Specialty section: This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience Received: 10 August 2021 Accepted: 10 March 2022 Published: 25 April 2022 Citation: Eyjolfsdottir H, Koenig T, Karami A, Almqvist P, Lind G, Linderoth B, Wahlberg L, Seiger Å, Darreh-Shori T, Eriksdotter M and Jelic V (2022) Fast Alpha Activity in EEG of Patients With Alzheimer’s Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor. Front. Aging Neurosci. 14:756687. doi: 10.3389/fnagi.2022.756687 Fast Alpha Activity in EEG of Patients With Alzheimer’s Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor Helga Eyjolfsdottir 1,2 , Thomas Koenig 3 , Azadeh Karami 1 , Per Almqvist 4,5 , Göran Lind 4,5 , Bengt Linderoth 4,5 , Lars Wahlberg 6 , Åke Seiger 7 , Taher Darreh-Shori 1 , Maria Eriksdotter 1,2 and Vesna Jelic 1,2 * 1 Department of Neurobiology, Care Science and Society, Karolinska Institutet, Solna, Sweden, 2 Theme Inflammation and Aging, Karolinska University, Stockholm, Sweden, 3 Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland, 4 Department of Clinical Neuroscience, Stockholm, Sweden, 5 Department of Neurosurgery, Theme Neuro, Karolinska University, Stockholm, Sweden, 6 NsGene Inc., Providence, RI, United States, 7 Stiftelsen Stockholms Sjukhem, Stockholm, Sweden Background: Basal forebrain cholinergic neurons are dependent on nerve growth factor (NGF) for growth and survival and these cells are among the first to degenerate in Alzheimer’s disease (AD). Targeted delivery of NGF has been suggested as a potential therapy for AD. This hypothesis was tested in a clinical trial with encapsulated cell biodelivery of NGF (NGF-ECB) in AD patients. Three of six patients showed improved biomarkers for cognition by the end of the study. Here, we report on the effects of targeted delivery of NGF on human resting EEG. Materials and methods: NGF-ECB implants were implanted bilaterally in the basal forebrain of six AD patients for 12 months. EEG recordings and quantitative analysis were performed at baseline, 3 and 12 months of NGF delivery, and analyzed for correlation with changes in Mini-mental state examination (MMSE) and levels of the cholinergic marker choline acetyltransferase (ChAT) in cerebrospinal fluid (CSF). Results: We found significant correlations between the topographic variance of EEG spectral power at the three study points (baseline, 3 and 12 months) and changes in MMSE and CSF ChAT. This possible effect of NGF was identified in a narrow window of alpha frequency 10–11.5 Hz, where a stabilization in MMSE score during treatment was related to an increase in EEG alpha power. A similar relation was observed between the alpha power and ChAT. More theta power at 6.5 Hz was on the contrary associated with a decrease in CSF ChAT during the trial period. Frontiers in Aging Neuroscience | www.frontiersin.org 1 April 2022 | Volume 14 | Article 756687