Here, we studied the association between the CSF p-tau/Aβ42 ratio with downstream markers of pre-clinical Alzheimer’s disease progression including brain structure, glucose metabolism, fibrillary Aβ deposition and cognitive performance in 234 cognitively unimpaired individuals, who underwent cognitive testing, a lumbar puncture, MRI, 18F-fluorodeoxyglucose and 18F-flutemetamol PET scanning. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.