title: Presenilin 2 mutation does not influence expression and concentration of APP forms in human platelets.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Pharmacological Sciences, University of Milano, Italy.
authors: L
authors: L
authors: Pastorino
authors: F
authors: F
authors: Colciaghi
authors: G
authors: G
authors: Marcon
authors: B
authors: B
authors: Borroni
authors: E
authors: E
authors: Cottini
authors: F
authors: F
authors: Cattabeni
authors: A
authors: A
authors: Padovani
authors: M
authors: M
authors: Di Luca
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D053766:Presenilin-2; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger