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While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.
Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.
Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.
“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.
“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.
Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.
The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.
The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.
Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.
The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.
These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.
“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”
Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.
Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”
At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.
Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.
“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.
Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”
And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.
Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”
On Twitter @Alz_Gal
While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.
Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.
Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.
“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.
“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.
Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.
The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.
The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.
Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.
The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.
These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.
“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”
Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.
Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”
At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.
Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.
“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.
Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”
And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.
Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”
On Twitter @Alz_Gal
While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.
Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.
Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.
“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.
“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.
Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.
The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.
The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.
Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.
The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.
These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.
“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”
Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.
Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”
At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.
Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.
“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.
Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”
And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.
Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”
On Twitter @Alz_Gal
