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Investigating such activity in human patients could lead to the identification of novel biomarkers of diagnostic and prognostic value. The current study aimed to test a multimodal \u201cPerturbation\u2010based\u201d transcranial Alternating Current Stimulation\u2010Electroencephalography (tACS)\u2010EEG protocol to detect how responses to tACS in AD patients correlate with patients' clinical phenotype.<\/jats:p><\/jats:sec>Methods<\/jats:title>Fourteen participants with mild to moderate dementia due to AD underwent a baseline assessment including cognitive status, peripheral neuroinflammation, and resting\u2010state (rs)EEG. The tACS\u2010EEG recordings included brief (6\u2032) tACS blocks of gamma (i.e., 40\u00a0Hz) stimulation administered through 4 different montages, with Pre\/Post 32\u2010Channels EEG for each block. Changes in tACS\u2010EEG and rsEEG \u03b3 band power with respect to baseline were adopted as a metric of induction and compared with cognitive scores and neuroinflammatory biomarkers.<\/jats:p><\/jats:sec>Results<\/jats:title>We found positive correlations between 40\u00a0Hz\u2010induced \u03b3 activity in fronto\u2010central\u2010parietal areas and patient cognitive status and negative ones with neuroinflammatory markers. Participants with greater cognitive impairment exhibited less \u03b3 induction and higher peripheral neuroinflammation. The same analysis performed with spectral power from baseline rsEEG resulted in no significant correlations, promoting the value of tACS\u2010based perturbation for capturing individual differences in pathology\u2010related brain features.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our work suggests a link between tACS\u2010induced \u03b3 band spectral power and clinical severity, with weaker \u03b3 induction corresponding to more severe clinical\/cognitive impairment. This study provides preliminary support for the development of novel physiological biomarkers and therapeutic targets based on disease severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gps.70025","type":"journal-article","created":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T13:53:49Z","timestamp":1736690029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preliminary Evidence for Perturbation\u2010Based tACS\u2010EEG Biomarkers of Gamma Activity in Alzheimer's Disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Annalisa","family":"Palmisano","sequence":"first","affiliation":[{"name":"Precision Neuroscience & Neuromodulation Program Gordon Center for Medical Imaging Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Berenson\u2010Allen Center for Noninvasive Brain Stimulation Department of Neurology Beth Israel Deaconess Medical Center Harvard Medical 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