Some prototypic degenerative dementias, such as Alzheimer’s disease and Lewy body disease, appear to be proteinopathies involving a multitude of neuronal phenotypes – and in some cases glia as well, as in the case of multisystem atrophy. These disorders involve a multiplicity of phenotypes, span both anatomic and functional domains as well, and may inexorably spread by both contiguous and trans-synaptic pathways within affected brains (Goedert, 2015; Kim and Holtzman, 2010; Luk et al., 2012a; Luk et al., 2012b). Alzheimer’s, mixed Alzheimer’s-Parkinson’s presentations, Lewy body disease, and multisystem atrophy are all examples of such conditions, and are all characterized by the transcellular propagation of pathogenic proteins, whether β-amyloid or alpha-synuclein. These disorders pose the shared challenges of a multiplicity of affected phenotypes, multicentric and diffuse pathology, and inexorable disease progression, through pathogenic mechanisms that are not readily modulated by cell replacement per se. These disorders would thus seem unlikely to benefit from any attempts at cell replacement-based treatment, whether neuronal or glial, at least until such time as we have learned enough about their mechanisms of pathogenesis to abrogate disease progression. Until then, these disorders would not seem especially apt targets for stem cell-based treatment approaches.
