Authors:

Ashli Evans

Date Created:

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About Paper:

Alzheimer's Disease (AD) is a degenerative brain disorder and the most common form of dementia. The presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), and loss of neuronal connections are hallmarks of this disease. Unfortunately, current therapies do not slow AD progression substantially, and the overwhelming majority of new, potential therapies fail in clinical trials. Major roadblocks for development of new, effective therapeutics for AD have been the lack of authentic animal models and our incomplete understanding of the pathological onset and progression of the disease. Gangliosidosis, a rare lysosomal disorder, is associated with ganglioside buildup in the brain, and there is much literature suggesting ganglioside-bound Aβ (GAβ) accelerates Aβ accumulation and is enriched within neurons of AD patients. Therefore, we hypothesize that gangliosidosis affected cats could be a novel model for studying progression of AD pathogenesis and for testing current and new AD therapies. We examined several different brain regions in gangliosidosis affected cats and age-matched controls for the presence and subtypes of amyloid plaques as well as distribution of phosphorylated Tau (pTau), the driver of NFT formation. Our results suggest that the plaques and NFTs in gangliosidosis cats correlate with AD progression. Specifically, plaques appear earlier in regions affected during early stages of AD, and increase in likelihood and number during the later stages of gangliosidosis in a manner comparable to later stages of AD. In addition, the progression of plaque subtypes and distribution of pTau throughout the brain of gangliosidosis cats may reflect the same pattern of progression in AD. Overall, our data support the hypothesis that gangliosidosis cats are a novel model for the study of AD pathogenesis and for the testing of AD therapies.

Source:

Auburn University / College of Veterinary Medicine / 2025

Topics:

No topics listed

Co-authors:

Ashli Evans