Similarly, in middle-aged rats, neither synthetic nor human/patient brain-derived Aβ facilitated LTD in the presence of etanercept (Fig. 6C and D), leading us to conclude that TNF-α could serve as a critical mediator of LTD-facilitating effects of tau and Aβ present in Alzheimer’s disease brain aqueous extracts. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.