Late-onset brain disorders, including dementia, have multiple causes. While some neurodegenerative diseases are inherited and caused by mutation in specific genes, others are sporadic and are associated with diverse risk factors. A common challenge in neurodegenerative diseases is the current lack of curative treatments, which underlines the urgent need for development of treatment therapies for our aging society. A detailed knowledge of the molecular mechanisms underlying the onset and progression of such diseases is of utmost importance to develop novel treatment strategies. Traditionally, protein aggregation of disease-causing proteins has been a central focus of research. To date, numerous studies addressed cellular pathogenic processes underlying dementia, revealing diverse cellular and molecular mechanisms contributing to neurodegeneration and disease development, besides protein aggregation and its consequences. One example of such emerging mechanisms is RNA-mediated toxicity of mutated, disease-causing transcripts in affected cell types. Another important aspect of neurodegeneration is the specific cellular pathologies of brain cells besides neurons, such as astrocytes and microglia. It becomes more and more evident that these, previously only considered supporting cells of neurons, develop cell type-specific phenotypes, which might precede the observed phenotypes in neurons.