Abstract
The pattern of platelet amyloid precursor protein (APP) forms is altered in sporadic Alzheimer's disease patients, compared with both control subjects and non-Alzheimer's disease-demented patients. The aims of this study were to evaluate in platelets of symptomatic and presymptomatic patients carrying the mutation Met239Val in presenilin 2 (PS2) whether: i) PS2 and presenilin 3 (PS1) were expressed in platelets; ii) an altered expression 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. Reverse transcriptionpolymerase chain reaction (RT-PCR) of APP isoforms, PS1 and PS2 was performed on RNA extracted from platelets of three PS2 Met239Val mutated subjects, seven sporadic Alzheimer's patients and nine control subjects. The pattern of platelet APP forms at protein level was evaluated in the same population of subjects by means of Western blots analysis with specific antibody. We found that PS1 and PS2 were expressed correctly in human platelets. When the relative amount of expression of mRNA coding for APP 771/ 751-695 was measured, a similar ratio of expression was found in PS2-mutated subjects, compared with both sporadic Alzheimer's patients and to control subjects. Furthermore, when APP forms were evaluated in platelet homogenates by means of Western blots analysis with appropriate antibody, no difference was found in the pattern of APP forms in presence of PS2 mutation in platelets, compared with control subjects. These results indicated that PS2 was expressed in human platelets and that PS2 mutation did not affect APP forms pattern, thus, suggesting that in this peripheral cell the pathological effect of PS2 mutation might occur upstream of the amyloid cascade.
Highlights
Accumulation of the amyloid- peptide (A) in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer’s disease (AD)
To assess the presence of mRNA coding for PS1 and PS2 in platelets, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis was performed in platelets obtained from patients carrying the PS2 mutation Met239Val (n ϭ 3), sporadic AD patients (n ϭ 7), and control subjects (n ϭ 7 matched for age, sex, and ethnicity with sporadic AD patients and two subjects of the Flo10 family not carrying the mutation)
Our study shows that human platelets express presenilins transcripts, with the level of PS2 expression lower relative to PS1 mRNA
Summary
Accumulation of the amyloid- peptide (A) in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer’s disease (AD). The pattern of platelet amyloid precursor protein (APP) forms is altered in sporadic Alzheimer’s disease patients, compared with both control subjects and non-Alzheimer’s diseasedemented patients. The aims of this study were to evaluate in platelets of symptomatic and presymptomatic patients carrying the mutation Met239Val in presenilin 2 (PS2) whether: i) PS2 and presenilin 3 (PS1) were expressed in platelets; ii) an altered expression 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. Conclusions: These results indicated that PS2 was expressed in human platelets and that PS2 mutation did not affect APP forms pattern, suggesting that in this peripheral cell the pathological effect of PS2 mutation might occur upstream of the amyloid cascade
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
