Distribution and progression of amyloid-β deposits in the amygdala of the aged macaque monkey, and parallels with zinc distribution

In this study, we have mapped amyloid β (Aβ) deposition in the amygdala of five aged Japanese monkeys (from 23 to 30 years old). In brief, the aged monkey amygdala shows a topographic distribution of Aβ deposits that is subnucleus specific and exhibits a distinct temporal progression. The pattern is similar to the distribution of Aβ deposits in the human amygdala of Alzheimer's patients and of high plaque nondemented cases. The spatial distribution and temporal progression were correlated with the distribution of free zinc (Zn), which is known to mediate Aβ aggregation. For the basolateral group of subnuclei in particular, there is a clear dorsoventral gradient in the progressive distribution of Aβ. Aβ depositions first appear in the ventral division of the lateral nucleus and parvicellular division of the accessory basal nucleus, and then extend into the ventral part of the basal and paralaminar nuclei. All these nuclei are also Zn-dense. Conversely, Zn-weak nuclei, which are more dorsally situated (i.e. dorsal division of lateral nucleus and magnocellular division of basal nucleus) showed only a low level of Aβ deposits, even in brains with the greatest Aβ burden. In contrast to the basolateral group, the central and medial nuclei and cortical group had Aβ deposits only at later stages. In the central and medial nuclei, we identified a lateromedial gradient of Aβ deposits, again similar to the gradient of Zn-distribution. In the cortical group, Aβ deposits are densest in the deep layer, where Zn is also densest. Thus, we suggest the macaque amygdala, with its clear topographic distribution of Aβ deposits, may be an effective model for examining the complex mechanisms of vulnerability to Aβ deposits. A primate model would be advantageous for experimental interventions geared toward therapeutic protection from Alzheimer's disease, including by microarray analysis and genetic manipulation.