We exploratively measured APPs alpha, a secreted fragment of the non-amyloidogenic cleavage of amyloid precursor protein via a-secretase, and tau protein phosphorylated at threonine 181 (ptau) in the cerebrospinal fluid of 10 patients with mild cognitive impairment, 20 patients with dementia of Alzheimer's type, and 10 controls. Cerebrospinal fluid APPs alpha and ptau levels were correlated with cognitive performance. Ptau levels were significantly elevated in mild cognitive impairment and in patients with dementia of Alzheimer's type, APPs alpha levels were significantly reduced in patients with dementia of Alzheimer's type compared to the controls. APPs alpha levels were associated with Mini Mental State Examination total scores but not with Delayed Verbal Recall Test performance. Vice versa, ptau levels correlated only with Delayed Verbal Recall Test in patients with dementia of Alzheimer's type or mild cognitive impairment. Both, an increase in ptau levels and a decrease in cerebrospinal fluid APPs alpha, seem to refer to relevant but functionally different processes in the development of mild cognitive impairment and dementia of Alzheimer's type.