Serum BDNF levels were significantly decreased in the AD group before AChE-inhibitors treatment (10 mg Donepezil per day) and significantly increased after 15 months of treatment with no more significant difference from the control group. Down-regulation of BDNF begins with the first clinical symptoms and becomes persistent in the AD continuum, while up-regulation of BDNF happens along with the neuroprotective effect of AChE-inhibitor. This evidence concerns the gene ACHE and Alzheimer disease.