RETRACTED ARTICLE: Increased Aβ 42 -α7-like nicotinic acetylcholine receptor complex level in lymphocytes is associated with apolipoprotein E4-driven Alzheimer’s disease pathogenesis

Background The apolipoprotein E ε4 ( APO E4) genotype is a prominent late-onset Alzheimer’s disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. Methods Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ) 42 -α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ 42 -α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APO E genotypes. Results In an ex vivo study using rodent synaptosomes, apoE 141–148 of the apoE promotes Aβ 42 -α7nAChR association and Aβ 42 -induced α7nAChR-dependent tau phosphorylation. In a single-blind study, we examined lymphocytes isolated from control subjects, patients with MCI and dementia due to AD with known APO E genotypes, sampled at two time points (1 year apart). APO E ε4 genotype was closely correlated with heightened Aβ 42 -α7nAChR complex levels and with blunted exogenous Aβ 42 effects in lymphocytes derived from AD and MCI due to AD cases. Similarly, plasma from APO E ε4 carriers enhanced the Aβ 42 -induced Aβ 42 -α7nAChR association in rat cortical synaptosomes. The progression of cognitive decline in APO E ε4 carriers correlated with higher levels of Aβ 42 -α7nAChR complexes in lymphocytes and greater enhancement by their plasma of Aβ 42 -induced Aβ 42 -α7nAChR association in rat cortical synaptosomes. Conclusions Our data suggest that increased lymphocyte Aβ 42 -α7nAChR-like complexes may indicate the presence of AD pathology especially in APO E ε4 carriers. We show that apoE, especially apoE4, promotes Aβ 42 -α7nAChR interaction and Aβ 42 -induced α7nAChR-dependent tau phosphorylation via its apoE 141–148 domain . These apoE-mediated effects may contribute to the APO E ε4-driven neurodysfunction and AD pathologies.