Genes of Early-Onset Alzheimers Disease EOAD

Mendelian Genes of Early-Onset Alzheimer s Disease (EOAD) 

Like APP mutations, the PS 1 and PS2 mutations can lead to increased levels of Ap brain. Whether the presenilins interact directly with APP through their putative y-secretase activity, or act as co-factor for another y-secretase, remains unclear. Furthermore, the relationship between identified causal mutations and AD phenotype is not necessarily simple. For example, PSl mutations associated with familial early-onset AD have been identified in individuals with frontotemporal dementia who have no evidence of the Ap accumulation characteristic of AD. 

While variants in these three genes (APP, PSl, and PS2) account for between 30% and 50% of early-onset familial AD, overall they account for less than 2% of all cases of AD (Klaver et al., 1998 Finckh et al., 2000 Liddell et al., 1995 Rosenberg et al., 2000). 

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