Hyperphosphorylated Tau Induces Cortical Hypoexcitability in Transgenic Mouse Models: A Meta-Analysis.

Background: Neurofibrillary tangles, composed of hyperphosphorylated tau, have been implicated in the cognitive impairments observed in Alzheimer's disease. While the precise mechanism remains elusive, cognitive deficits in Alzheimer's disease have been associated with disrupted brain network activity. To investigate this mechanism, researchers have developed several tau transgenic models. However, the extent of variability in cortical network alterations across different genetic backgrounds and ages is still not clearly defined.

Objective: To evaluate the oscillatory alterations in relation to animal developmental age and hyperphosphorylated tau protein accumulation, we reviewed and analyzed the published data on peak power and quantification of theta-gamma cross-frequency coupling (modulation index values).

Methods: A systematic review was conducted to locate and extract all studies published from January, 2002 to March, 2024 involving in vivo cortical local field potential recording in tau transgenic mouse models, ensuring the most current search results. Our meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.

Results: The presence of hyperphosphorylated tau was associated with oscillatory alterations primarily reflected in power decreases, while modulation index values did not exhibit significant alterations.

Conclusions: In this analysis, we uncovered that neuronal oscillations in cortical networks are altered from the prodromal to late stages of pathology. Additionally, we found that hyperphosphorylated tau accumulation is strongly associated with cortical network hypoexcitability in tau transgenic models.