Research with human primary neuron cultures to identify a molecular pathway of neurodegeneration associated with cognitive impairment has revealed that the sequential activation of inflammasome Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing 1 (Nlrp1), Caspase-1 (Casp1), and Caspase-6 (Casp6) by serum deprivation or over-expression of wild-type (WT) and familial AD-associated mutant amyloid precursor protein (APP) is associated with amyloid-beta (Aβ)-independent loss of neuron structure and function and Aβ-dependent neuronal cell death [1–4]. Here, CASP6 is linked to Cognitive impairment.