When expressed within stressed neurons, apoE4 is cleaved, to a much greater extent than apoE3, into neurotoxic fragments that disrupt the cytoskeleton and impair mitochondrial functions. Tau, which is normally most abundant in axons, becomes mislocalized to the neuronal soma and dendrites and forms inclusions called neurofibrillar tangles (NFTs). α-synuclein can also self-assemble into pathogenic oligomers and form larger aggregates (Lewy bodies). Both tau and α-synuclein can also be released into the extracellular space, where they may spread to other cells. Vascular abnormalities impair the supply of nutrients and removal of metabolic byproducts, cause microinfarcts, and promote the activation of glial cells.