# Spontaneous mammalian models for Alzheimer's disease and dementia

## TL;DR

This review explores non-laboratory animal models that spontaneously develop Alzheimer's-like features, suggesting they could improve understanding of dementia.

## Contribution

The paper identifies non-laboratory animals as potential models for Alzheimer's disease due to their spontaneous amyloid plaque formation.

## Key findings

- Companion, farm, and marine mammals develop amyloid plaques and some hyperphosphorylated tau.
- Few non-human animals develop neurofibrillary tangles or neuronal loss like in human Alzheimer's.
- These models may better represent specific aspects of Alzheimer's if further developed.

## Abstract

Globally, the human population is ageing, and, consequently, the prevalence of major neurocognitive disorders is increasing, resulting in a greater need for novel dementia therapeutic interventions. Animal models are invaluable in studying underlying pathological processes in human diseases and with evidence for rising life expectancy in many domesticated animals studies have investigated neurocognitive disorders in several non-human species. Rodents have been used extensively as animal models, but this review will examine published literature suggesting candidate non-laboratory animal models for studying dementia, especially human Alzheimer's disease. Comparison of the physiological, pathological and clinical features of companion animals, farm animals and marine mammals shows that although many animals develop amyloid plaques and, to lesser degree, hyperphosphorylated tau protein, very few develop neurofibrillary tangles or neuronal loss to the same extent as humans with Alzheimer's disease. Several hypotheses are proposed as to why, as yet, no animals have been found to spontaneously develop Alzheimer's disease-like pathology to the same level as humans but highlight specific aspects where these models may be useful if developed further.

No laboratory animal model fully reproduces Alzheimer's disease. However, companion (dogs, cats, horses), farm (cattle, sheep, pigs, donkeys) and marine mammals (odontocetes, pinnipeds) spontaneously develop amyloid plaques and, to lesser degree, hyperphosphorylated tau. Therefore, these species may be more representative models of specific aspects of Alzheimer's disease if developed further.

Graphical Abstract