Apolipoprotein E4 as a Novel Treatment Target for Alzheimer’s Disease

The importance of Alzheimer’s Disease (AD) research has never been greater from a worldwide perspective with the disease becoming increasingly prevalent with life expectancy on the rise. One emerging factor that has presented as a serious risk that still requires more research and understanding is the role and effects of Apolipoprotein E4 (ApoE4). When present, individuals are three times more likely to develop AD in their lifetime. This is due to ApoE4’s ability to not only increase amyloid beta plaque aggregation ApoE4 also increases hyperphosphorylation of tau causing neurofibrillary tangles. These two factors are the well-known hallmarks for AD, which increase the importance for ApoE4 research as it affects both major aspects. Treatment for AD has always been an issue due to a variety of factors with only a few approved for use today. These approved treatments are only to ease and supress symptoms rather than treating the disease. Dementia symptoms such as memory loss, language problems, motor skills, irritability and paranoia are all symptoms that destroy patient’s ability to function in their communities. Inhibiting ApoE4 and reducing its toxic effects is a promising theory that has the ability to extend AD patients’ lifespan and prolong capable brain function limiting brain tissue degradation.

Effect of Apolipoprotein E4 on the Driving Behavior of Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer’s Disease Dementia

Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. Conclusion: The lower speed variability of APOE4 carriers in the absence of neuropsychological test differences indicates reduced speed adaptations, possibly as a compensatory strategy. Simulated driving may be a sensitive method for detecting performance differences in the absence of cognitive differences.