BACKGROUND: Similarities between Alzheimer disease (AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent. OBJECTIVE: To investigate APOE's role in PD using family-based association analyses. METHODS: APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD. RESULTS: APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD. CONCLUSIONS: The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.
BACKGROUND: Similarities between Alzheimer disease (AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent. OBJECTIVE: To investigate APOE's role in PD using family-based association analyses. METHODS:APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD. RESULTS:APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD. CONCLUSIONS: The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.
Authors: D W Tsuang; R K Wilson; O L Lopez; E K Luedecking-Zimmer; J B Leverenz; S T DeKosky; M I Kamboh; R L Hamilton Journal: Neurology Date: 2005-02-08 Impact factor: 9.910
Authors: Shinsuke Fujioka; Christina Sundal; Audrey J Strongosky; Monica Case Castanedes; Rosa Rademakers; Owen A Ross; Carles Vilariño-Güell; Matthew J Farrer; Zbigniew K Wszolek; Dennis W Dickson Journal: Acta Neuropathol Date: 2012-11-04 Impact factor: 17.088
Authors: Karsten Bartels; Yi-Ju Li; Yen-Wei Li; William D White; Daniel T Laskowitz; Miklos D Kertai; Mark Stafford-Smith; Mihai V Podgoreanu; Mark F Newman; Joseph P Mathew Journal: Can J Anaesth Date: 2015-03-06 Impact factor: 5.063
Authors: Yi-Ju Li; Margaret A Pericak-Vance; Jonathan L Haines; Nailah Siddique; Diane McKenna-Yasek; Wu-Yen Hung; Peter Sapp; Coy I Allen; Wenjie Chen; Betsy Hosler; Ann M Saunders; Lisa M Dellefave; Robert H Brown; Teepu Siddique Journal: Neurogenetics Date: 2004-10-02 Impact factor: 2.660
Authors: Kristoffer Haugarvoll; Mathias Toft; Lisa Skipper; Michael G Heckman; Julia E Crook; Alexandra Soto; Owen A Ross; Mary M Hulihan; Jennifer M Kachergus; Sigrid B Sando; Linda R White; Timothy Lynch; J Mark Gibson; Ryan J Uitti; Zbigniew K Wszolek; Jan O Aasly; Matthew J Farrer Journal: Eur J Hum Genet Date: 2008-10-15 Impact factor: 4.246