Spatial orientation deficits are emerging as very early and reliable cognitive biomarkers predicting future memory problems associated with Alzheimer’s disease, but the neural mechanisms underlying spatial disorientation have yet to be fully defined. The anterodorsal thalamic nucleus (ADn) contains a high density of head direction (HD) cells, which play a critical role in the brain's ability to create and update spatial representations, aiding in navigation and spatial memory. We propose that the accumulation of Tau filaments in cell bodies, dendrites, and axons of HD cells disrupts the processing of head direction orientation signals in the ADn and its connected regions, explaining why individuals become disoriented in preclinical Alzheimer’s disease. Using extracellular recordings and juxtacellular labelling in awake mice, we defined single HD cells in the ADn based on their axonal projections and postsynaptic targets, along with HD-related firing patterns. Mice with virally-expressed human mutant Tau locally in ADn neurons show a trend towards impaired spatial memory performance, which might be attributed to the reduced number of HD cells in the ADn and their less specific directional coding. These findings will contribute to our understanding of the mechanism of the HD signal pathway in humans, aiding in the detection and interpretation of early deficits in spatial navigation in individuals with mild cognitive impairment.