Hutchinson-Gilford progeria syndrome (HGPS) is a fatal disorder involving the appearance of accelerated aging in young children. HGPS is caused by a mutation in the lamin A gene, LMNA, the study of which has provided fundamental insights into basic cellular biology and the biology of normal aging. Cellular consequences of lamin dysfunction in progeria and other “laminopathies” resulting from mutations in LMNA include invaginations and herniations of the nuclear envelope and relaxation of heterochromatic DNA. The segmental nature of progeria has been a longstanding mystery in aging research: certain aspects of aging appear to be recapitulated in the syndrome, while others, particularly neurodegeneration, are not. We have found that acquired lamin misregulation though aberrant cytoskeletal-nucleoskeletal coupling mediates neuronal death in a Drosophila model of Alzheimer's disease and related tauopathies. In addition, we observed robust alterations in the nuclear lamina in neurons from patients with Alzheimer’s disease. To demonstrate definitively that lamin dysfunction can promote brain aging, we depleted lamin function genetically in the Drosophila nervous system and observed markedly decreased lifespan accompanied by age-dependent neurodegeneration. Our findings challenge the paradigm that the brain is resistant to lamin dysfunction, and identify new avenues for the therapeutic treatment of Alzheimer’s disease and related tauopathies.