Updated project metadata. Alzheimer’s disease (AD) is the most common neurodegenerative disorder being characterized by progressive impairment of memory and cognition, resulting in dementia. To investigate brain region vulnerability to AD and which pathways are altered in certain areas in AD, we performed proteomic profiling of human brain samples during AD progression in regions early (medial temporal lobe - MTL) and late affected (neocortex) by tau pathology. We employed a mass spectrometry-based approach to interrogate the human brain proteome during AD progression (B/B stages) in four distinct brain regions: entorhinal cortex (EC), parahippocampal cortex (PHC), temporal cortex (TC) and frontal cortex (FC). Importantly, we wanted to evaluate brain areas that are affected by tau pathology in different disease stages, in order to gain insights if there are common mechanisms or patterns shared between different brain regions during disease progression. A total of 103 samples were analyzed by nanoLC-MS/MS.