Elevated Platelet β-Secretase Activity in Mild Cognitive Impairment

Abstract

Background/Aims: We have recently reported that platelet activity of the rate-limiting enzyme for β-amyloid peptide production is elevated in established Alzheimer’s disease. Laboratory investigation of the very early stages of dementia provides an opportunity to investigate pathological mechanisms before advanced disease hinders interpretation. Mild cognitive impairment (MCI) exists prior to obvious dementia, and is associated with increased risk of conversion to overt disease. Methods: We developed and used a fluorimetric assay to quantify platelet membrane β-secretase activity in 52 patients with MCI and 75 controls. Results: Platelet membrane β-secretase activity was 24% higher in individuals with MCI compared to controls (p = 0.001, unpaired t test with Welch correction). Conclusion: Elevated platelet β-secretase activity in subjects with MCI is an area for further study in relation to the etiology and diagnosis of MCI.

Platelet Alpha- and Beta- Secretase Activities are not Significantly Affected by Dementia or Mild Cognitive Impairment in Swedish Patients

“…One group has recently reported elevated platelet -secretase activity in AD and MCI [22] [27]. However, within our population we failed to demonstrate a significant effect of AD or MCI on either of the two activities or the ratio between the two activities.…”

Platelets, a reliable source for peripheral Alzheimer’s disease biomarkers?

“…In addition, an increased activity of β-secretase was indirectly shown by a decreased ratio of its 37/56 kDa fragments from two different groups [143, 144]. Another group determined it directly by an enzymatic assay with a 17% elevation in activity in AD platelets [41] and with an even more pronounced 24% upregulation in MCI platelets [42]. The concentration of β-secretase cleavage products was also found to be significantly increased [145].…”

Platelet Alpha- and Beta- Secretase Activities are not Significantly Affected by Dementia or Mild Cognitive Impairment in Swedish Patients

“…There was a higher proportion of female subjects in the healthy control group than the MCI or AD groups (Table 1) but there was no significant effect of gender on the platelet secretase activity in any of the groups when tested using Students two tailed t-Test. The patients sampled in this study had a range of MMSE score (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), indicating relative heterogeneity in terms of disease progression (Table 1).…”