Portal de Periódicos da CAPES

P1–319: Presenilin 2 Ser130Leu mutation in a case of late–onset “sporadic” AD

2006; Wiley; Volume: 2; Issue: 3S_Part_7 Linguagem: Inglês

10.1016/j.jalz.2006.05.697

1552-5279

Carmine Tomaino, Livia Bernardi, Maria Anfossi, Angela Costanzo, Francesca Ferrise, Maura Gallo, Silvana Geracitano, Raffaele Maletta, Sabrina A.M. Curcio, Maria Mirabelli, Rosanna Colao, Francesca Frangipane, Gianfranco Puccio, Cinzia Calignano, Maria Gabriella Muraca, Annamaria Paonessa, Nicoletta Smirne, Attilio Leotta, Amalia C. Bruni,

Advanced biosensing and bioanalysis techniques

Mutations of PSEN2 gene are a rare cause of Familial Alzheimer's Disease (FAD) displaying a large span of the age at onset (40–80 years). To date, PSEN2 mutations have never been described in sporadic late onset AD. The PSEN2 Ser130Leu mutation, signalled as pathogenic and causative in a patient from a dominant FAD family, has recently been interpreted, after in vitro experimental procedures, as a rare polymorphism or a mutation not pathogenic. To report the PSEN2 Ser130Leu mutation in a sporadic late onset AD case. Patient manifested his mild memory deficits, spatial disorientation and personality changes at 81. At 83 diagnosis of AD was performed according to NINCDS–ADRDA criteria, neuropsychology, and neuroimaging. No cases of dementia were reported in his family, however, his father and one sister, both deceased at 84 without cognitive decline, were referred as having had a “Parkinson's disease” (PD). Although it did not matter, the family asked for molecular screening of the known FAD genes. All available relatives were also genetically investigated. 220 unrelated subjects (110 controls and 100 AD patients) were screened for Ser130Leu mutation through PCR–RFLP and sequence analyses respectively. Apolipoprotein E was also genotyped. Sequence analysis identified a PSEN2 Ser130Leu mutation in exon 5 that was present also in two out of three of his healthy children and it was absent in all 220 subjects screened, excluding it as common polymorphism. APOE genotype was ϵ3ϵ3. The PSEN2 Ser130Leu mutation found in our “sporadic” AD late onset case and in the previously reported one is not a common polymorphism. For what concerns the pathogenicity of the mutation, it is obviously possible that in vivo other genetic and/or environmental factors could interact with the mutation to produce the pathological phenotype. In our patient neither a de novo nor an inherited mutation can be ruled out. Each of his parents could have transmitted it without developing AD if their death occurred before the onset. Indeed, frequency of PSEN2 mutations could be underestimated in AD general population.