Abstract
A genetic association of an intronic single nucleotide polymorphism site of heparan sulfate proteoglycan 2 (HSPG2) with Alzheimer's disease (AD) was investigated among Finnish AD patients ( n =213) and controls ( n =269). No association of the HSPG2 polymorphism alone was observed with AD. However, an association of HSPG2 A allele with AD was detected in apolipoprotein (APOE) ε4 allele carriers. The odds ratio for AD was doubled in subjects carrying both ε4 and HSPG2 A alleles (OR=6.6) when compared to subjects with ε4 allele alone (OR=3.1). The impact of HSPG2 polymorphism on beta amyloid and tau pathology was studied using immunohistochemistry. Paired helical filament labeling was significantly more pronounced in AD patients carrying both ε4 and HSPG A alleles when compared to ε4 carriers lacking the HSPG2 A allele. In conclusion, HSPG2 A allele may possess an additive risk effect among the APOE ε4 carriers in AD.
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