ALZHEIMER'S DISEASE
A main goal of our activity is the prevention, treatment and diagnosis of neurodegenerative diseases. In recent years, we have developed technological tools for the recording of electroencephalography and electromyography signals in animals without restriction of movement and without anestesia. We have also characterized behavioral states (wake/sleep cycle) by semiautomatic scoring.
In this area we aim to study cerebral rhythms and cycle sleep-awake stages in mouse models of Alzheimer´s disease, searching for abnormal patterns of activity with valuable potential as biomarkers for early diagnosis in the clinics. Although the objective is defined within the framework of Alzheimer's disease, results obtained in this topic and technological tools can be implemented in other neurodegenerative disorders, such as Huntington's or Parkinson´s diseases; since multiple evidences relate neurodegeneration with sleep wake cycle abnormalities during preclinical and prodromal diagnosis.
(A) Representative coronal section of a 9-month-old 5XFAD mouse brain stained with Thioflavin S showing amyloid plaques marked in green. Amyloid deposits reach a very large burden especially in deep cortical layers (Cx), hippocampus (Hp) and thalamus (Th). (B) Cognitive deficits (spatial memory) examined with the Y-maze spontaneous alternation test in the 5XFAD mouse model of Alzheimer’s disease. Fernández-García et al. 2016. Safety and tolerability of silk fibroin hydrogels implanted into the mouse brain. doi: 10.1016/j.actbio.2016.09.003.
Representative EEG epoch of a 5 month-old 5XFAD mouse during wake and its correponding EMG signal. The mouse had free movement while recording.
Early neuronal hyperexcitability and altered phase-amplitude coupling (PAC) in young 5XFAD mice. (A) Relative HFO power (100-500 Hz) in young and adult WT and 5XFAD mice. Increased HFO power is already present in young 5XFAD mice, indicating early neuronal hyperexcitability prior to substantial amyloid plaque accumulation. (B) ROC curve analysis evaluating the discriminative power of relative HFO power between WT and 5XFAD genotypes in young and adult groups. High AUC values demonstrate that HFO power serves as a highly effective classifier across both ages. (C) Phase-amplitude coupling (PAC) comodulograms mapping average dPAC values across phase and amplitude frequencies in young WT and 5XFAD mice. White contours outline identified regions of interest, highlighting an emerging high-frequency coupling zone (Y3*) unique to the 5XFAD group. (D) Mean relative dPAC within the Y3* ROI (left) and relative power in the fast ripple band (250–500 Hz, center) are significantly elevated in 5XFAD mice, showing a strong positive Pearson's correlation (right). This demonstrates that compromised theta-HFO coupling is detectable at a pre-plaque stage and directly correlates with pathological fast ripple activity. García-Peña et al. 2026. Slow-wave–modulated high-frequency oscillations reveal early network abnormalities in pre-pathological 5XFAD mice doi: 10.1016/j.nbd.2026.107484