Presenilin gene mutations in familial early-onset Alzheimer’s disease

The highly homologous presenilin-1 (PS1) and -2 (PS2) genes are found on chromosomes 14 and 1, respectively. Both genes encode cellular proteins with at least 7 transmembrane (TM) spanning domains. The PS1 and PS2 genes are predominantly expressed in neurones and glia, and while their exact function is unknown, mutations of these genes are implicated in the development of familial early-onset Alzheimer’s disease (AD). Mutations of the PS1 gene account for about 70% of all early-onset cases. More than 40 causative mutations have been found in the PS1 gene, while only 3 have been identified in PS2. One residue is mutated in both presenilins and this is the N135 (PS1)/N141(PS2) residue. It is unclear how mutations in the presenilins cause AD, but evidence suggests they have a role in amyloid precursor protein (APP) processing and apoptosis.

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References

Hum Mol Genet 1997;6:1639–1646.