Different Aβ43 deposition patterns in the brains of aged dogs, sea lions, and cats

Abstract

Cerebral amyloid β (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). There are several molecular species of Aβ, including Aβ40, Aβ42, and Aβ43, and the pathological roles of Aβ43 have attracted particular attention in recent years.Aβ43 is mainly deposited as senile plaques (SPs) in AD brains, and is known to be more amyloidogenic and neurotoxic than Aβ42 and Aβ40. Aβ40 and Aβ42 deposition have been demonstrated in several animal species, while Aβ43 deposition has not been studied in animals. The brains of sea lions, dogs, and cats exhibit unique age-related Aβ pathologies. In the present study, the deposition patterns of Aβ40, Aβ42, and Aβ43 were examined immunohistochemically in the brains of aged dogs (n=52), sea lions (n=5), and cats (n=17). In dogs, most cerebral amyloid angiopathy (CAA) lesions and primitive SPs were positive for Aβ42, Aβ43, and Aβ40. However, diffuse SPs and capillary CAA lesions were negative for Aβ40. In sea lions, all SPs and most CAA lesions were positive for Aβ42, Aβ43, and Aβ40, while capillary CAA lesions were negative for Aβ40. In cats, Aβ42-immunopositive granular aggregates and arteriole and capillary CAA lesions were positive for Aβ43, but negative for Aβ40. Double-labelling immunohistochemistry revealed the co-localization of Aβ42 and Aβ43. These findings suggest that Aβ43 and Aβ42 are frequently deposited in the brains of Carnivora animals and may play an important role in Aβ pathology.

Senile plaques and phosphorylated tau deposition in a super-aged rhesus monkey (<i>Macaca mulatta</i>)

“…The present case suggests that Aβ43 deposition may be involved in Aβ plaque formation in rhesus monkeys, as well as humans and other animals. Aβ43 deposition in CAA was more pronounced in capillaries than in cortical small arteries, consistent with the dogs and sea lions [25]. This might be because Aβ43 may aggregate in upstream of the intramural periarterial drainage pathway [29], which is strongly related to CAA, as in dogs and sea lions [25].…”

“…The brain tissue sections were subjected to immunohistochemistry (IHC) using primary antibodies shown in Supplementary Table 1. The scoring system for parenchymal Aβ deposition in Table 1 was prepared with reference to Chambers et al [3], and Takahashi et al [25]. Congo red and Thioflavin S stainings showed a large number of SPs throughout the cerebral cortex (Table 1, Fig.…”

“…[ 3 ], and Takahashi et al . [ 25 ]. Congo red and Thioflavin S stainings showed a large number of SPs throughout the cerebral cortex ( Table 1 , Fig.…”

“…In addition to Aβ40 and Aβ42, Aβ43 has recently been found to have aggregation potential [ 4 ] and toxicity [ 2 , 21 ]. Aβ43 deposition in SPs of animals has been reported in gorillas, dogs, cats, and sea lions [ 10 , 25 ]. The present case suggests that Aβ43 deposition may be involved in Aβ plaque formation in rhesus monkeys, as well as humans and other animals.…”

Going beyond established model systems of Alzheimer’s disease: companion animals provide novel insights into the neurobiology of aging

“…In humans, the deposition of Aβ1–42 (but not Aβ1–40) increases with age in AD 203 , 204 . Dogs also have more Aβ1–42 than Aβ1–40 in their plaques, but mature plaques, with their dense Aβ1–40 cores, appear less commonly than in humans 205 – 211 . However, like humans, both cats and dogs have Aβ1–40 deposits in cerebral and meningeal blood vessels (Supplementary Data 2 125 , 200 , 212 ) that may lead to CAA 213 .…”