Fig. 3.

Mechanisms involved in apoE-related neurodegeneration. The influence of the APOE genotype has been associated with CNS diseases such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Traumatic Brain Injury (TBI), Stroke, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). In particular, APOE4 promotes synaptic impairment, amyloid-β (Aβ) protein seeding, aggregation, Aβ-plaque formation and defective protein clearance in AD. APOE4 will contribute to additional pathological features characteristic of AD, but also present in other CNS pathologies such as, for instance, impairment of the autophagy/endosomal system, altered microglial reactivity and neuroinflammation, and blood–brain barrier disruption