{"doi":"10.1002/gps.70025","title":"Preliminary Evidence for Perturbation‐Based tACS‐EEG Biomarkers of Gamma Activity in Alzheimer's Disease","abstract":"BACKGROUND: Alzheimer's disease (AD) is characterized by impaired inhibitory circuitry and GABAergic dysfunction, which is associated with reduced fast brain oscillations in the gamma band (γ, 30-90 Hz) in several animal models. 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 \"Perturbation-based\" transcranial Alternating Current Stimulation-Electroencephalography (tACS)-EEG protocol to detect how responses to tACS in AD patients correlate with patients' clinical phenotype. METHODS: Fourteen participants with mild to moderate dementia due to AD underwent a baseline assessment including cognitive status, peripheral neuroinflammation, and resting-state (rs)EEG. The tACS-EEG recordings included brief (6') tACS blocks of gamma (i.e., 40 Hz) stimulation administered through 4 different montages, with Pre/Post 32-Channels EEG for each block. Changes in tACS-EEG and rsEEG γ band power with respect to baseline were adopted as a metric of induction and compared with cognitive scores and neuroinflammatory biomarkers. RESULTS: We found positive correlations between 40 Hz-induced γ activity in fronto-central-parietal areas and patient cognitive status and negative ones with neuroinflammatory markers. Participants with greater cognitive impairment exhibited less γ 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-based perturbation for capturing individual differences in pathology-related brain features. CONCLUSIONS: Our work suggests a link between tACS-induced γ band spectral power and clinical severity, with weaker γ 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.","journal":"International Journal of Geriatric Psychiatry","year":2025,"id":540064,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1427954,"name":"Luke R. Pezanko","orcid":null,"position":1,"is_corresponding":false},{"id":312353,"name":"Davide Cappon","orcid":"0000-0002-0326-2191","position":2,"is_corresponding":false},{"id":312352,"name":"Elisa Tatti","orcid":"0000-0002-7137-550X","position":3,"is_corresponding":false},{"id":647413,"name":"Joanna Macone","orcid":null,"position":4,"is_corresponding":false},{"id":106046,"name":"Giacomo Koch","orcid":"0000-0001-6155-9439","position":5,"is_corresponding":false},{"id":1034334,"name":"Carmelo Luca Smeralda","orcid":"0000-0001-5331-9400","position":6,"is_corresponding":false},{"id":312351,"name":"Sara M. Romanella","orcid":"0000-0002-7202-5421","position":7,"is_corresponding":false},{"id":255921,"name":"Giulio Ruffini","orcid":"0000-0003-3084-0177","position":8,"is_corresponding":false},{"id":1427511,"name":"Davide Rivolta","orcid":"0000-0002-9969-9135","position":9,"is_corresponding":false},{"id":646863,"name":"Daniel Z. Press","orcid":"0000-0001-6401-1305","position":10,"is_corresponding":false},{"id":106052,"name":"Álvaro Pascual‐Leone","orcid":"0000-0001-8975-0382","position":11,"is_corresponding":false},{"id":727962,"name":"Georges El‐Fakhri","orcid":null,"position":12,"is_corresponding":false},{"id":106059,"name":"Emiliano Santarnecchi","orcid":"0000-0002-6533-7427","position":13,"is_corresponding":false},{"id":1034333,"name":"Annalisa Palmisano","orcid":"0000-0003-4193-534X","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:52:34.520788Z","pmid":"39799469","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}