Presenilin 2 mutation does not influence expression and concentration of APP forms in human platelets

Background: The pattern of platelet amyloid precursor protein (APP) forms i s altered in sporadic Alzheimer's disease patients, compared with both cont rol subjects and non-Alzheimer's disease-demented patients. The aims of thi s study were to evaluate in platelets of symptomatic and presymptomatic pat ients carrying the mutation Met239Val in presenilin 2 (PS2) whether: i) PSZ and presenilin 3 (PS1! were expressed in platelets: ii) an altered express ion of different APP isoforms mRNAs could be related to the presence of the mutation; and iii) an abnormal pattern of APP forms was associated to the mutation. Materials and Methods: Reverse transcription-polymerase chain reaction (RT- PCR) of APP isoforms, PSI and PS2 was performed on RNA extracted from plate lets of three PS2 Met239Val mutated subjects, seven sporadic Alzheimer's pa tients and nine control subjects. The pattern of platelet APP forms at prot ein level was evaluated in the same population of subjects by means of West ern blots analysis with specific antibody. Results: We found that PS1 and PS2 were expressed correctly in human platel ets. When the relative amount of expression of mRNA coding for APP 771/751- 695 was measured, a similar ratio of expression was found in PSZ-mutated su bjects, compared with both sporadic Alzheimer's patients and to control sub jects. Furthermore, when APP forms were evaluated in platelet homogenates b y means of Western blots analysis with appropriate antibody, no difference was found in the pattern of APP forms in presence of PS2 mutation in platel ets, compared with control subjects. Conclusions: These results indicated that PS2 was ex-pressed in human plate lets and that PS2 mutation did not affect APP forms pattern, thus, suggesti ng that in this peripheral cell the pathological effect of PSZ mutation mig ht occur upstream of the amyloid cascade.