The progressive invasion of the brain by neurofibrillary tangles characterized by paired helical filaments (PHF) along a precise network is stereotypical and hierarchical from normal aging to severe Alzheimer's disease. We describe here the differential expression of genes in the temporal area with PHF compared with the occipital area non-affected by PHF in cases with cognitive impairment versus the same cortical regions of control human brains without PHF. A stronger overexpression for 14-3-3 zeta gene is demonstrated in the affected temporal cortex of cases with cognitive impairment than in cases with normal mental status. This data obtained directly from human brains confirmed a 14-3-3 zeta implication in the Alzheimer's neuropathology.