Fig. 2. Alzheimer’s disease is associated with a specific range of pathologies, which emerge at different ages in different species.

a Major hallmarks of AD include brain atrophy, plaques, and tangles (NFTs). b The disease is characterized by a leaky blood-brain barrier. Normally, astrocytes form tight junctions, so much so that these barriers formed by astrocytes prevent the entry of materials into the brain. In AD, the blood-brain barrier is compromised, and the disease is also characterized by vacuoles and neuronal death. c There is a stereotypic sequence in the accumulation of brain plaques and tangles starting in the olfactory cortex and hippocampus, which then spread through most of the brain. The early accumulation of plaques and tangles in the olfactory cortex is concomitant with the loss of olfactory abilities. We compare the timeline of brain plaques and tangles in cats (d) and macaques (e). Cats may accumulate plaques and tangles for a relatively long percentage of their life. Many reports indicate that cats can develop plaques and tangles and cognitive dysfunction before the age of 10, but similar deficits are more likely expected to occur in macaques in their 20s^38,174. Cats recapitulate the hallmarks of aging relatively early and so may be an ideal model system of aging. Dashed lines represent a probability of occurrence and are based on qualitative reports from the literature (see Supplementary Data 2)¹²⁵.