Abstract
Elderly cats develop age-related behavioral and neuropathological changes that ultimately lead to cognitive dysfunction syndrome (CDS). These neuropathologies share similarities to those seen in the brains of humans with Alzheimer’s disease (AD), including the extracellular accumulation of ß-amyloid (Aβ) and intraneuronal deposits of hyperphosphorylated tau, which are considered to be the two major hallmarks of AD. The present study assessed the presence and distribution of Aβ and tau hyperphosphorylation within the cat brain (n = 55 cats), and how the distribution of these proteins changes with age and the presence of CDS. For this, immunohistochemistry was performed on seven brain regions from cats of various ages, with and without CDS (n = 10 with CDS). Cats accumulate both intracytoplasmic and extracellular deposits of Aβ, as well as intranuclear and intracytoplasmic hyperphosphorylated tau deposits. Large extracellular aggregates of Aβ were found in elderly cats, mainly in the cortical brain areas, with occasional hippocampal aggregates. This may suggest that these aggregates start in cortical areas and later progress to the hippocampus. While Aβ senile plaques in people with AD have a dense core, extracellular Aβ deposits in cats exhibited a diffuse pattern, similar to the early stages of plaque pathogenesis. Intraneuronal Aβ deposits were also observed, occurring predominantly in cortical brain regions of younger cats, while older cats had few to no intraneuronal Aβ deposits, especially when extracellular aggregates were abundant. Intracytoplasmic hyperphosphorylated tau was found within neurons in the brains of elderly cats, particularly in those with CDS. Due to their ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the neurofibrillary tangles seen in AD. The largest numbers of pre-tangles are found mainly in the cerebral cortex of elderly cats, whereas lower numbers were found in other regions (i.e., entorhinal cortex and hippocampus). For the first time, intranuclear tau was found in both phosphorylated and non-phosphorylated states within neurons in the cat brain. The highest numbers of intranuclear deposits were found in the cortex of younger cats, and this tended to decrease with age. In contrast, elderly cats with pre-tangles had only occasional or no nuclear labelling.
Highlights
In humans, age-related brain changes, such as brain atrophy, neuronal loss, and vascular pathology, may lead to dementia and Alzheimer’s disease (AD) (Raz, 2004; Jack et al, 2005; Glabe, 2006)
This study shows that elderly cats develop both Aβ and tau pathologies; with large extracellular Aβ deposits and the presence
Cats of all ages had extracellular Aβ deposits; the extent of these deposits varied between age groups
Summary
Age-related brain changes, such as brain atrophy, neuronal loss, and vascular pathology, may lead to dementia and Alzheimer’s disease (AD) (Raz, 2004; Jack et al, 2005; Glabe, 2006). The abnormal deposition of senile plaques containing ß-amyloid (Aβ) and neurofibrillary tangles (NFT) composed of hyperphosphorylated tau are major pathognomonic neuropathologies of AD, and are thought to play a key role in its development (Hardy and Allsop, 1991; Thal et al, 2002; Perl, 2010). While the neuropathology of this condition is still poorly understood, several age-related neurodegenerative changes (i.e., brain atrophy, neuronal loss, vascular changes, and abnormal protein deposition) are found in the brains of elderly cats (Head et al, 2005; Gunn-Moore et al, 2006). While Aβ40 is the most abundant and tends to accumulate within blood vessels, Aβ42 tends to accumulate in the extracellular space and form the characteristic senile plaques of AD (Hardy and Allsop, 1991; Perl, 2010)
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