Domenico Mordà, Luigi Donato, Simona Alibrandi, Concetta Scimone, Alessandra Costa, Fabiana Nicita, Rosalia D’Angelo, Antonina Sidoti
Summary
Alzheimer-Perusini’s disease is the most common dementia underlying pathology around the world. Although it relies on a series of well-known pathognomonic hallmarks (i.e., β-amyloid plaques and neurofibrillary tangles), many doubts remain about its etiopathogenesis. As happened with other little-known diseases, genetics might shed lights on its mechanisms of occurrence. The aim of this review is discussing about genetic studies in this field, without neglecting an assessment of their relative relevance. Hence starting from a comparison between GWAS analysis and little family study, we will describe the pathogenic role of six gene in Alzheimer-Perusini’s disease pathogenesis. Three of these (SORL1, ABCA7 and BIN1) are involved in endolysosomal trafficking and processing of amyloid precursor protein (APP). Another one, ABI3 is relevant for cellular chemiotactic movement, for example the directed displacement of microglia aimed at β-amyloid fibrils phagocytosis. In addition, we covered CLU/APOJ (a particular apolipoprotein) functioning, that seems to be essential for plaques clearence. Finally, we described also ADAMTS1 a metalloproteinasis, which acts on Aβ in extracellular environment. In particular, we have mentioned some genetic peculiarities of the atypical forms, which probably represent the most interesting Alzheimer-Perusini’s pathology subset, because of its high (more than mendelian ones), but not very high (less than sporadic forms) number of associated gene, which also corresponds to an intermediate environmental influence.
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