The rs‐gamma connectivity alterations related to the atrophy pattern and CSF p‐tau in early‐onset AD

Abstract

AbstractBackgroundAmong the other frequencies, the gamma frequency has received the least attention in the study of Alzheimer’s disease (AD). Previous studies point to association between amyloid accumulation and gamma alterations, suggesting that gamma activity may serve as a potential biomarker for the pathophysiology of AD. The goal of the current study is to examine changes in resting‐state (rs) gamma activity in patients with CSF‐proven early‐onset AD (EOAD) and their relationship to structural pathology associated with the disease.MethodDrug‐naive CSF‐proven EOAD patients [mean age: 57.92 (4.35) years] and age‐, gender, and education‐matched healthy controls (HC) [mean age: 57.58 (4.01) years] were included. Gamma imaginary part of coherency (ICoh) was measured in total gamma (30‐48 Hz), gamma‐1 (30‐35 Hz), gamma‐2 (35‐40 Hz), and gamma‐3 (40‐48 Hz) frequencies. Gray matter volumes compared between groups. The rsEEG gamma activity was used for discriminant analysis. The relationships between rsEEG, MRI, and CSF p‐tau measurements were investigated.ResultIn the EOAD group, gray matter volume in temporal, parietal, and occipital areas were decreased by over 20%. We discovered that the volume of frontal and neighboring regions, that were intact in this patient group, was negatively correlated with F8‐TP8 and F4‐C4 ICoh of sub‐gamma bands. On the contrary, the volume of temporal and parietal regions where the atrophy was prominent, was positively correlated with P8‐O2 and C3‐O1 ICoh of sub‐gamma bands. In the EOAD, executive function and F7‐TP7, P3‐O1 sub‐gamma bands were negatively correlated.Regarding CSF, p‐Tau and C3‐C4 gamma‐1 showed strong positive correlation (r = 0.615). Lastly, a set of gamma ICoh measurements displayed a correct classification rate of 83% between groups.ConclusionGamma coherence follows pair‐specific alterations related to atrophy pattern in EOAD. The gamma connectivity becomes greater where atrophy is increased and when CSF p‐tau is higher in EOAD. This study establishes the significance of sub‐gamma oscillations as a non‐invasive biomarker candidate with achieving an 83% correct classification rate between groups.