Alzheimer’s is relentless and so are we. The Alzheimer’s Association was founded in 1980 by a group of family caregivers and individuals who recognized the need for an organization that would unite caregivers, provide support to those facing Alzheimer’s and advance research into the disease. Over the last forty years our mission has not changed; and we are much closer to our goal.

As we all know, there is currently no FDA approved intervention to cure, slow or prevent the onset of Alzheimer’s. But as both the workshop and these essays highlighted, we have made significant strides towards developing new treatments.

This is because of the steady accumulation of knowledge and understanding of the disease and its progression. And as our knowledge has accumulated, Alzheimer’s research has identified many diverse biological targets of Alzheimer’s, beyond the hallmark presentations of β-amyloid plaques and tau tangles. Recent advancements in how understanding and measuring the emerging pathology of disease, thinking about the disease as a continuum, developing tools to actively monitor disease-related changes in a living person, and new strategies for identifying and enrolling participants in clinical trials as well as confirmation of drug target engagement, means the pace of accumulated knowledge is increasing. And this means that today we stand are on the cusp of a new paradigm.

There are two factors I would highlight that have been important in making advances in the field to get us to this point – and remain important in advancing research. They are firstly the funding and the effective use of that funding, and secondly, collaboration.

As the largest nonprofit funder of Alzheimer's and dementia research in the world the Association provides direct funding to researchers, including supporting and expanding the AD drug development pipeline. Currently, the Association is investing over $208 million in 590 active best-of-field projects in 31 countries. These studies are targeting a wide variety of known and potential new aspects of the disease, such as inflammation and other promising new targets for therapy.

The Association has advocated for increased federal funding that has been critical over the last decade. In a polarized Washington we have developed and grown bipartisan support for critical policy priorities. Over the last decade the funding for the National Institutes of Health (NIH) for Alzheimer’s research has increased from $450 million to $2.8 billion annually. As of fiscal year 2020, Congress agreed a $350 million year-on-year increase. As a result of these significant increases, scientists are able to work at a more rapid pace to advance basic disease knowledge, explore ways to reduce risk, uncover new biomarkers for early diagnosis and drug targeting, and develop potential treatments.

As in the United States, globally we have seen increases in Alzheimer’s research funding. As a community we need to continually champion the critical importance of that funding. As a field, proportionate to impact and need it remains underfunded compared to other disease areas.

Nationally and internationally, we need to ensure that we have maximum impact for ever dollar we raise, or the taxpayer contributes. The Association has worked closely with the National Institute on Ageing (NIA) since our founding, collaborating in funding and recruiting participants for several flagship clinical trials. In 2011, workgroups

jointly convened by the Association and the NIA issued new diagnostic guidelines for Alzheimer's disease and proposed a research agenda to define a new preclinical stage of the disease. In 2018, the Association and the NIA convened once again to publish a new Research Framework that proposes the use of biomarkers to detect Alzheimer’s in its earliest stages.

One of the lessons I draw from the Covid-19 pandemic is the importance of scientific collaboration in accelerating progress. The sharing of knowledge, the building of relationships. The Alzheimer’s Association International Conference (AAIC), the world’s largest and most influential international meeting dedicated to advancing dementia science. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) that brings together scientists, physicians and other dementia professionals active in researching and understanding the causes and treatments of Alzheimer's disease and other dementias.

Alongside this we partner with key government, industry and academic stakeholders through a number of forums include ADNI, GAAIN, AMP-AD and GBSC to build collaboration. The Alzheimer's Association Research Roundtable, a consortium of scientists from the pharmaceutical, biotechnology, diagnostics, imaging and cognitive testing industries, and scientists from the NIH, FDA, European Medicines Agency, Health Canada and other government agencies, who seek to facilitate the development and implementation of new treatments.

Funding and collaboration are why we have been instrumental to making the progress we have and will be key in the years ahead. There are many challenges ahead. There is a significant gap in funding the identification and development of potential drugs before they are tested in humans. And there is a need for funding to bridge this gap, departing from traditional funding mechanisms by combining both expertise with the necessary know-how with the needed resources to translate more potential therapies to human studies. We must advance all potential treatment avenues and also explore methods

for combining these approaches. Alzheimer’s and other dementias are complex, and their effective treatment and prevention will likely also be a complex – but achievable – task. All currently pursued treatments that are considered safe should be continued to determine their efficacy.

While there are many challenges to development of therapies for Alzheimer’s and other dementia, the Alzheimer’s Association has never been more optimistic than it is today.

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Dr Maria Carrillo is chief scientific officer, Alzheimer’s Association.

This piece appears in an essay collection about biomarkers and treatments, reflections from international leaders in dementia on the conversations had during and after the dementia landscape project global dialogue event.