TARDBP and proteostasis deficiencies: The other 45% of patients with MCI have a negative amyloid scan; therefore, they can be classified as “non-AD pathologic change” or “suspected non-AD pathophysiology.” This latter group might include participants with primary age-related tauopathy, hippocampal sclerosis, TDP-43 (TAR DNA-binding protein 43) pathology, primary progressive aphasia, or cerebrovascular disease.32 In both amyloid- and nonamyloid-driven neurodegeneration, microglial activation could have an important role in modulating propagation of proteinopathies.