Génétique de la maladie d'Alzheimer : formes autosomiques dominantes

We propose a review devoted to the autosomal dominant forms of Alzheimer disease (AD). These forms are the consequences of either PSEN1 mutations (69%), APP mutations (1%), or APP duplication (7.5%), and exceptionally of PSEN2 mutations (2%). The main characteristic of these AD forms is the early age of onset usually before the age of 60 years. The first part of the review focuses on the identification of unusual clinical and neuropathological phenotypes enlarging the AD spectrum: intracrebral hemorrhages caused by severe amyloid angiopathy, spastic paraparesis, Lewy body dementia and exceptional cerebellar ataxia. The second part concerns the consequences of these mutations on Aβ processing, thus demonstrating the key role of the causal “amyloid cascade”.