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Title: Beta-secretase activity in huaman blood platelets in patients and relationships to polymorphisms in BACE in Alzheimer's disease and control subjects.
Author: Todd, S. A.
ISNI:       0000 0001 3534 3319
Awarding Body: Queens University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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This study aimed to investigate whether there are differences in the ~-secretase activity in the platelets of Alzheimer's disease (AD) subjects and cognitively normal control subjects and to determine whether the concentration of cholesterol influences this activity. A further aim was to study whether the apolipoprotein (ApoE) £4 allele or polymorphisms in the ~-site amyloid precursor protein cleaving enzyme (BACE1) gene are associated with AD or with alterations in the ~-secretase activity in platelets. METHODS: Subjects with a diagnosis of AD (NINCDS - ADRDA) were recruited from a regional Memory Clinic. Control subjects with no evidence of cognitive impairment were also recruited. Blood samples were drawn for assay of ~-secretase activity and genetic analyses. Statistical analysis was performed using SPSS for Windows version 14, GraphPad version 4, and HaploView version 4. RESULTS: 399 SUbjects were recruited; 201 with probable AD and 198 controls. Mean platelet membrane ~-secretase activity was significantly higher in the AD group, compared to the control group. Age and serum cholesterol concentration were significantly higher in the AD group, but did not correlate with the platelet membrane ~-secretase activity. Platelet membrane cholesterol concentration was significantly lower in the AD group and was significantly positively IlI I, I I' I~ I I! ---------------------- correlated with the platelet membrane ~-secretase activity. ApoE £4 was strongly associated with AD but did not correlate with the platelet membrane ~-secretase activity. Variation in the BACE1 gene was not associated with AD and did not correlate with the platelet membrane ~-secretase activity. CONCLUSIONS: Platelet membrane ~-secretase activity is elevated in AD and is correlated with the platelet membrane cholesterol concentration. Common variants in the BACE1 gene do not influence the genetic susceptibility for AD in the NI population.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available