The team of ADDF scientists who attended last week’s virtual Alzheimer’s Association International Conference (AAIC 2020) were energized by some very exciting research news and the opportunity to exchange ideas with other leading Alzheimer’s researchers and clinicians from all over the world. Here are their top five takeaways from AAIC 2020.
Breakthrough Alzheimer’s blood test on the horizon
An international study reported that a new blood test can very accurately predict who has Alzheimer’s disease, even before cognitive symptoms appear. This blood test measures a specific type of tau protein called p-tau217 and could be available as early as next year. The simple diagnostic test could be a real game changer, replacing more costly and invasive PET scans and spinal taps that today are the only way to conclusively diagnose Alzheimer’s in living patients.
While the p-tau217 blood test looks like it will be the first to market, additional tests are likely to follow based on many other exciting presentations at AAIC. Researchers reported positive findings about blood tests for other forms of tau protein that may signal neurodegeneration in the brain, and also reported on targets beyond traditional amyloid and tau proteins. These included markers of inflammation and emerging protein biomarkers like neurofilament light polypepetide (NfL) and glial fibrillary acidic protein (GFAP).
As the ADDF often says, the path to finding effective Alzheimer’s treatments starts with better ways to diagnose patients. Earlier detection using blood tests is critical because it will help ensure the right people are enrolled in clinical trials and provide a better way to assess outcomes.
The biology of aging takes center stage
The ADDF has long championed an approach to Alzheimer’s that translates the biology of aging, the number one risk factor for the disease, into new treatments. In a session on repurposing existing drugs, the ADDF’s Founding Executive Director and Chief Science Officer Howard Fillit, MD discussed the role of senescent cells, which are highly correlated with aging, and a first-of-its-kind trial targeting these cells in people with the Alzheimer’s.
These so-called “zombie cells” activate internal programs that help them avoid their natural death cycle. But instead of functioning normally, these senescent cells release toxins that damage nearby healthy cells. The toxins promote a host of age-related pathways that are implicated in Alzheimer’s disease, such as increased inflammation.
A phase 2, placebo-controlled trial led by Miranda Orr, PhD at Wake Forest School of Medicine, which the ADDF is supporting, is one of the first to explore using senolytic agents in patients with Alzheimer’s disease. Senolytics selectively target senescent cells and keep them from undergoing programmed cell death. The trial will test a combination of repurposed senolytic drugs – dasatinib, which is used to treat leukemia, and quercetin, an anti-inflammatory supplement.
Increasing emphasis on FTD research
There was an increase in new reports of preclinical, clinical and biomarker research related to frontotemporal dementia (FTD), a rare, rapidly progressive form of early-onset dementia most common for people under age 60. One exciting area of research focuses on drugs targeting mutations in the progranulin gene, which is associated with increased inflammation and death of cells in the brain.
Alector reported on phase 1b/2 trials of its candidate antibody drug AL001, which blocks the degradation of progranulin. Both trials reported that the antibody is generally safe and well tolerated, which was their primary endpoint. The small phase 1B open-label trial of 14 people also measured biomarker responses. AL001 restored progranulin levels to the normal range in cerebrospinal fluid and there was a positive trend of reduction in NfL levels in plasma. AL001 also normalized other biomarkers of inflammation and lysosomal activity, which is essential in the body’s ability to degrade and recycle proteins. The phase 2 trial is ongoing but has been delayed by Covid--19. AL001 has received orphan drug and fast track status from the FDA, which are reserved for drugs that treat serious conditions where this is a large unmet need.
The ADDF has invested in progranulin research through its Accelerating Drug Discovery for FTD program, managed in partnership with The Association for Frontotemporal Degeneration. This investment supports the work of Thomas Kukar, PhD at Emory University in Atlanta, who is developing a strategy to replace the faulty protein in patients with progranulin gene mutations.
Autophagy may provide new therapeutic avenues for Alzheimer’s drug development
In the first plenary talk of AAIC 2020, Dr. Ralph Nixon, Director of Research at NYU’s Center for Dementia Research, discussed the growing interest among Alzheimer’s researchers in autophagy, a recycling and cleanup process that rids the body of damaged and misfolded proteins.
Brain diseases like Alzheimer’s involve clumps of toxic proteins, and autophagy needs to function normally to clear these clumps away.
The ADDF supports the development of new therapies targeting autophagy through its partnership with Harrington Discovery Institute and other funding mechanisms and has prioritized funding additional research into this emerging area.
New studies on dementia and Alzheimer’s prevention
New data and recommendations presented at AAIC expand understanding about delaying the onset of, or even preventing, dementia. The Lancet Commission on Dementia Prevention, Intervention and Care added three new risk factors for dementia to their list—excessive alcohol use or brain injury in mid-life and exposure to air pollution in later life. This brings the total to 12 modifiable risk factors the Commission says can delay or prevent 40 percent of dementia cases.
The nine previously identified risk factors are less education early in life; hearing loss, high blood pressure, and obesity in mid-life; and smoking, depression, social isolation, physical inactivity, and diabetes later in life.
Three studies presented at this year’s conference support the Commission’s findings. High blood pressure, diabetes, and heart-related health factors among Blacks during early life were associated with cognitive deficits in later life. Being overweight or obese in early adulthood (age 20-49) was also associated with higher risk of dementia later in life, especially for women. Higher quality early-life education, in contrast, was associated with a reduced risk of late-life dementia.
In articles written by the ADDF’s team of in-house neuroscientists, our Cognitive Vitality website has explored how Alzheimer’s affects different populations, including in our recent blog African Americans and Alzheimer’s Disease.
It is clear from these meeting highlights and recent advances in the field that the future of Alzheimer’s research is here. Significant progress is being made in the development of better diagnostics and drug treatments – giving renewed hope for the millions of families who are impacted by this devastating disease. The ADDF is proud to play a significant part in advancing the science in pursuit of finding a cure.