Several studies propose it is the sequence of onset and progression of amyloid and tau pathologies,95-97 whilst others suggest that neuronal loss is the most important pathological feature.41,98-100 Furthermore, loss of synapses is considered to be the strongest correlate of cognitive decline in Alzheimer's disease.101-104 As the primary proteinopathies in Alzheimer's disease, amyloid and tau accumulations represented by Aβ plaques and NFTs, respectively, have been the primary focus of studies of pathology relating to neurodegeneration in ageing animals (Table 3). This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.