It has been established that smell impairment is a common early feature of neurodegenerative diseases (NDs), being most prevalent in Alzheimer’s disease patients. As well as in other brain regions, the deposition of pathological substrates such as amyloid peptides (Aβ) or the hyperphosphorylated form of tau has been suggested as a potential origin of olfactory deficits. Nevertheless, other trends of thought are now suggesting the detriment in the soluble forms of these proteins as potentially responsible of the neurodegenerative process. Either way, the molecular mechanisms triggered by the presence and aggregation of these pathological substrates are not fully understood. In this chapter, we describe a workflow combining the use of neuropathological substrates depicting a neurodegenerative environment in an olfactory-related context with the employment of protein arrays targeting both extracellular and intracellular proteins aiming to characterize the molecular mechanisms underlying the established role of neuropathological hallmarks.