Does it describe a new discovery, methodology, or synthesis of knowledge?

In 1906, Dr. Alois Alzheimer described the neuropathological changes that now confirm the devastating neurological disorder that takes his name. These lesions in the brain are known as "plaques" and "tangles" and for a hundred years have been cited as the cause of the neuronal loss and memory dysfunction that characterize AD.

“Our findings provide hope. Translation of our work from mice to humans would suggest that the cause of AD will be identified sooner rather than later.”

Our manuscript described experiments using a transgenic mouse model of human dementia. The data we presented in SantaCruz et al. revealed two important discoveries. For the first time, we showed that memory loss similar to that in patients with AD is reversible. In addition, our data categorically showed that the "tangles" were not the cause of memory loss in the mice.

These findings represent a significant advance in the study of AD and offer hope that further progress will follow. Our data showed that neurofibrillary tangles (NFT) are not the cause of memory loss. This is important, as it shifts the focus of AD research towards the cause rather than a resulting lesion.

We suggested that NFTs represent a neuroprotective cellular strategy. Critically, future research may identify the molecule that precedes NFT formation and underlies memory dysfunction. This data will reveal a viable molecular target for the pharmacological treatment of AD and other age-related neurodegenerative disorders.

I became interested in the role of tau in memory loss when several groups in the years 1999 and 2000 showed that NFT-forming transgenic mice expressing tau variants develop neurodegeneration, a prominent aspect of AD pathology that was missing in amyloid plaque–forming transgenic mice.

Our initial attempts to create a model with regulatable transgenes spanned several years and were not overtly productive. When we finally succeeded, in 2002, our rTg4510 mouse became the platform for a meeting of minds in the laboratories of Mike Hutton at the Mayo Clinic in Jacksonville, Brad Hyman at Massachusetts General Hospital, Boston, and our group. This was critical because the work could not have been carried out by only one of our groups.

At one point, I thought the whole project had gone awry because I was expecting memory function to deteriorate as NFT accumulated. I was depressed for a while because the data went against my preconceived ideas. However, my spirits lifted when I realized that the data suggested the existence of tau*, a molecule which, like Aβ*56 (Lesné et al., Nature, 2006), could impair memory function independently of amyloidosis or neuronal death.

AD is the fourth biggest killer in economically developed countries. Currently, the cause of AD of is unknown and there is no cure or effective treatment available. In the United States alone there are over four million people with AD, costing an estimated one billion dollars a year. A growing population and increased life expectancy predict that this figure will balloon over the next decades, presenting a massive social and economic challenge.

Our findings provide hope. Translation of our work from mice to humans would suggest that the cause of AD will be identified sooner rather than later. Moreover, our data imply that memory loss in humans is reversible, providing the greatest hope of all. For the first time we can imagine reversing the symptoms of AD instead of preventing or merely slowing the progress of disease.