A large ApoE ε4/ε4 homozygous cohort reveals no association with Parkinson’s disease

Abstract

To investigate the correlation between cognitive impairment, Parkinson's disease (PD) symptoms and ApoE ε4/ε4 homozygosity an ApoE ε4/ε4 homozygous cohort was compared with an ApoE ε3/ε3 homozygous comparison group. A total of 696 outpatients with memory complaints had undergone comprehensive neuropsychiatric assessment including interview and examination by clinical psychiatrists and neurologists as well as laboratory blood testing (including ApoE genotyping). Patients also underwent the Consortium to Establish a Registry on Alzheimer's Disease (CERAD) test battery and the Clock-Drawing Test (Shulman scoring). Of the 623 selected individuals 258 were homozygous for ApoE ε3 and 133 were homozygous for ApoE ε4, while 232 were heterozygous for ApoE ε3/ε4. Thirty patients in the entire sample were diagnosed with PD (4.8 %). In the ApoE ε4/ε4 group seven persons had PD (5.3 %), while in the ApoE ε3/ε3 comparison group nine persons were diagnosed with PD (3.5 %). In the ApoE ε3/ε4 heterozygous group we found 14 (6.03 %) subjects meeting criteria for PD, P = 0.406. This is to our knowledge the largest retrospective cohort study to date of ApoE ε4 homozygous carriers. In comparison with the ApoE ε3 homozygous carriers in our study, subjects who were homozygous for ApoE ε4 demonstrated a slightly but statistically insignificant higher prevalence of PD, while in the ApoE ε3/ε4 heterozygous group we detected the highest rate of probands diagnosed with PD. We conclude that there is no correlation between allele combinations of ApoE ε3 and ApoE ε4 in their heterozygote and homozygote composition and prevalence of PD.

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

“…During memory encoding, we found reduced brain activity within the temporo-parietal network and impaired performance in carriers of APOE4 . Although the number of APOE4 carriers was small, this observation is consistent with the literature (Pulkes et al , 2011; Domenger et al , 2012; Federoff et al , 2012; Peplonska et al , 2013; Multhammer et al , 2014). It has been suggested that APOE4 Parkinson’s disease carriers present more severe cortical atrophy (Wakabayashi et al , 1998; Li et al , 2004) and more frequent cognitive decline than patients without an APOE4 allele (Irwin et al , 2012).…”

“…Finally, apolipoprotein E ( APOE ) has been proposed to alter the risk of Parkinson’s disease dementia (Chen et al , 2004; Huang et al , 2006; Goris et al , 2007; Williams-Gray et al , 2009 b ; Chung et al , 2012; Gomperts et al , 2012, 2013) as well as being a risk factor for Alzheimer’s disease, even if it does not significantly alter the risk of developing Parkinson’s disease without Parkinson’s disease dementia (Peplonska et al , 2013; Multhammer et al , 2014). APOE has three allelic variants ( APOE2 , 3 and 4 ), and APOE4 carries the highest risk for Alzheimer’s dementia (Corder et al , 1993) with APOE2 carrying the lowest.…”

Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement

“…Studies evaluating a possible association of APOE risk alleles with PD or with cognitive decline in PD have shown conflicting results [62e65]; APOE ε4 was found not to be associated with progression of PD to cognitive decline or dementia previously [62,64], but a recent, larger study reported such an association [65]. Even if the APOE ε4 allele does not significantly alter the risk of developing PD [63,66,67], accumulating evidence confirms that APOE ε4 is an important predictor of cognitive function in PD across multiple cognitive domains [59] including the memory domain [65,68].…”

Role of Apolipoproteins and α-Synuclein in Parkinson’s Disease

“…This suggests that apoEε4 may be a risk factor for PD in people with lower genetic variation (Blázquez et al 2006 ). However, some other studies show no differences in apoE genotypes (Federoff et al 2012 ; Multhammer et al 2014 ). In one study, PD patients with dementia (PDD) had two-fold higher apoEε4 allele content than normal people, suggesting a role for apoEε4 in PDD (Parsian et al 2002 ).…”