Twenty-one unrelated patients with a history of suspected familial Alzheimer disease (FAD) were screened for mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP). The mutation detection rate was 57%. Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S). Whereas our findings suggest the possibility of single founders for the majority of mutations, we found evidence of recurrence of the APP mutations V717L and V717I.

Metabotropic glutamate receptors alter the vulnerability of neurons to excitotoxic damage and are reported to display abnormal expression in the central nervous system of ALS patients. Using reverse transcriptase polymerase chain reaction, we investigated the mRNA expression of specific metabotropic glutamate receptor subtypes in T lymphocytes of 20 patients with sporadic ALS, compared with healthy age-matched control subjects and patients with other neurological disorders. The levels of metabotropic glutamate receptor 2 mRNA were markedly reduced, whereas the expression of other subtypes (1b, 3, 8) was similar to control levels. Our findings may provide a reliable peripheral marker of the glutamatergic dysfunction that characterizes ALS.

No abstract