Cats as a Model for Alzheimer’s Disease

Larry and I have had 17 or so felines as members of our household. Babycat was the only one to be diagnosed with dementia.

One of our daughters had brought Babycat home from a party. She and her sisters named him Babycat because he was a kitten, not realizing he would not always be so, and would wind up somewhere in the middle of our cat roster.

In his later years, Babycat took to howling piteously at a corner of our bedroom ceiling, every early evening and sometimes during the night too. We assumed he was responding to mice scurrying across the attic floor.

But Babycat was likely sundowning. And shortly after, our vet said Babycat probably had dementia. We became accustomed to the plaintive howling.

Now researchers from the University of Edinburgh’s Royal School of Veterinary Studies and the UK Dementia Research Institute have published in The European Journal of Neuroscience findings of their investigation of dementia in felines. The brain changes are remarkably similar to those of people with Alzheimer’s disease, suggesting that cats could augment studies using mouse models.

“Feline dementia is so distressing for the cat and for its person. It is by undertaking studies like this that we will understand how best to treat them. This will be wonderful for the cats, their owners, people with Alzheimer’s and their loved ones. Feline dementia is the perfect natural model for Alzheimer’s, everyone benefits,” said researcher Danièlle Gunn-Moore.

Toxic Protein Buildup in the Brain

Babycat apparently was suffering from “feline cognitive dysfunction syndrome” – aka feline dementia. This “age-related neurodegenerative disorder” includes, in addition to the increased vocalization, altered social interactions and sleep–wake cycle, disorientation, and peeing outside the box.

Feline brains of kitties like Babycat have a build-up of the toxic protein amyloid-beta – one of the two proteins in excess and with altered distribution in the human Alzheimer’s brain.

The study describes “increased vocalization – or meowing,” confusion, and disrupted sleep – also like people with Alzheimer’s disease (except of course the meowing). If you’ve had cats a long time, it’s easy to pick up on altered behavior, like sleep patterns and anxiety.

The investigators studied the brains of 25 cats of different ages after they had passed away, including those with signs of dementia.

Powerful microscopy revealed build-up of amyloid-beta plaques in the synapses – the tiny spaces that neurotransmitters traverse between neurons in the brain – of older cats and cats with symptoms of dementia. Disrupting synaptic transmission eats away at brain structure and function – and memory and cognition falter. Two sizes of amyloid beta normally accumulate outside neurons, but the smaller pieces are cleared away before they can do harm.

A second protein that’s part of the Alzheimer’s picture is Tau, which builds up inside brain neurons. Typically tau maintains the distinctive form of the elongated nerve cell, fringed with dendrites at one end, the taillike axon at the other. When tau accumulates in an Alzheimer’s brain, neuron structure collapses. And the toxic proteins ultimately eat away at blood vessels in the brain too.

But that’s not all. The researchers also discovered that other types of brain cells – astrocytes and microglia – engulf and destroy affected synapses in cat brains. This synaptic pruning is part of normal prenatal development, but when skewed, lies behind autism spectrum disorder (too many brain neuron connections) and schizophrenia (too few connections). This article delves into the molecular details of an Alzheimer’s brain.

Alzheimer’s Mice

Mice have been the gold standard for animal models of Alzheimer’s disease. The Jackson Lab in Bar Harbor, Maine – ground zero for biomedical research using mouse models – runs the JAX Center for Alzheimers and Dementia Research. Rodents genetically modified to have human genes serve as models, but these mammals do not typically develop dementia, possibly because they don’t live long enough to do so. (Remember cats have nine lives.)

So cats are clearly a better model organism due to their biology, but also because their humans become so adept at detecting altered behavior, such as meowing at a spot on the ceiling. I’ve had pet rodents and never observed a behavior other than eating, peeing, and breeding, although my escaped rat Vladimir once bit my husband on the rear as he slept. Vlad became snake food shortly thereafter.

I hope that cats can help us better understand Alzheimer’s.

“Dementia is a devastating disease – whether it affects humans, cats, or dogs. Our findings highlight the striking similarities between feline dementia and Alzheimer’s disease in people. This opens the door to exploring whether promising new treatments for human Alzheimer’s disease could also help our ageing pets. Because cats naturally develop these brain changes, they may also offer a more accurate model of the disease than traditional laboratory animals, ultimately benefiting both species and their caregivers,” concluded lead investigator Robert McGeachan.

CODA
Another intriguing phenotype amongst the Lewis cats was Marbles, a tailless domestic shorthair who did not like me, but loved my daughter Carly. When Marbles’ behavior suddenly altered, and she tilted and staggered, Carly convened a group of friends to sit in a circle and croon to the faltering feline. We took Marbles to the vet, fearing a brain tumor, but it turned out to be a brainworm – and l can’t help but wonder if it was the same type living inside the cranium of RFK Jr.