Apoe genotype influences the biological effects of AChe inhibitors on platelet APP metabolism

A. Padovani, B. Borroni, F. Colciaghi, L. Pastorino, L. Rozzini, E. Cottini, R. Monastero, G. L. Lenzi, F. Cattabeni, M. Di Luca

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Abstract

Background. Three major amyloid precursor protein (APP) forms with molecular weights of 130, 110, and 106 KDa are present in human platelets. Alzheimer disease (AD) is associated with a decrease in APP form ratio between the three major forms. Design/methods. Among a large sample of probable AD patients, 25 mild to moderate AD patients were selected. Each patient underwent a clinical evaluation, including the Mini-Mental State Examination (MMSE) and Apo E isoform dosage. Platelet APP form analysis was performed before (T0) and after 30 days (T30). Fifteen out of 25 AD patients were investigated after a 30-days period on Donepezil treatment (5 mg/die) (AD-T). Platelets were subjected to Western blot analysis, using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher MW APP form (130 kDa) and the lowest forms (106-110 kDa) was calculated. Results. All patients on Donepezil completed the 30-day treatment without adverse side effects. Platelets APP form ratio at baseline did not differ between the two AD groups (AD controls = 0.47 ± 0.12; AD-T= 0.38 ± 0.18) whereas a significant difference was found at follow-up (AD control s= 0.45 ± 0.17; AD -T = 0.77 ± 0.29) (P <0.001). Although a significant improvement in MMSE scores was observed from TO to T30 (mean ± SD; MMSE T0=16.9 ± 3.8, MMSE T30 = 18.9 ± 4.42, P <0.009) in the AD-T group, no significant association was found between improvement of MMSE scores and increase in APP ratio. Eight AD-T patients were E4 carriers whereas 7/15 were E3/E3. No significant difference in platelet APP ratio was found between the AD-T subgroups at T0, although the mean change was significantly higher in E3/E3 (P <0.001). By ANOVA, a significant group × treatment interaction was found with regard to APP ratio (P <0.01) favoring E3/E3 carriers. Conclusion. The present study provides direct evidence that AChEI administration increases the ratio of APP forms in platelets of AD patients and confirms the clinical efficacy of AChEI as symptomatic agents. These findings argue for a potential ApoE-related biological effect of AChEIs on those pathogenic mechanisms involved in AD, suggesting a new way of understanding the molecular basis of AD.

Original languageEnglish
JournalNeurological Sciences
Volume21
Issue number4 SUPPL.
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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