[Music] greetings Bill Mobley for on our mind presentation of uctv here at UCSD um our sessions on Alzheimer's disease have taught us that early diagnosis is an very important objective of making a difference in people's lives that later diagnoses May well be confounded by difficulty in reversing pathology or preventing it and in that context genetically predisposed populations are very important for understanding Alzheimer's disease and learning how to treat it and one such population is the Down Syndrome population with me again is Mike rafy who is the head of the adult Down syndrome clinic at uh
UCSD in the department of neurosciences Mike welcome again tell us about your work in this very interesting Clinic thanks Bill so the Down Syndrome Clinic is really an extension of the Down Syndrome research and treatment center and essentially it allows us to provide care to individuals with Down Syndrome who may be experiencing early onset Alzheimer's disease uh as you mentioned about 2% of all Alzheimer's cases are uh familial and early onset the remaining cases are occurring in patients over the age of 72 and have a usual progression but in younger individuals there is a more
aggressive uh uh process that takes place and a more rapid deterioration a lot of individuals with Down Syndrome are highly at risk for developing Alzheimer's Disease by virtue of the fact that the gene for amalo precursor protein uh is on the 21st chromosome and all individuals with Down Syndrome have an extra copy of the 21st chromosome and therefore an extra copy of this Gene leading to over production of this protein typically patients by the age of 12 or 13 years old start to have plaques amalo plaques in their brain so that by the age of
40 100% of individuals with Down Syndrome Harbor the plaques and Tangles of Alzheimer's disease the changes that occur in the brain once those plaques and Tangles build up include deficits and chemicals in the brain neurotransmitters but also shrinkage or atrophy of the same areas of the brain that are observed in the genetic forms of Alzheimer's disease as well as sporadic Alzheimer's disease so genetically defined Alzheimer's disease is due to a gene or uh in some group of genes that in families or in individuals with Down Syndrome basically make the disease happen earlier and perhaps more
aggressively that's correct but in fact if you look at those tissue sections if you're a neuropathologist it looks like they look the same in other words the Alzheimer's disease that you see in these genetically predisposed populations mimics and very much resembles what happens in those of us who don't have a family history that's exactly right in fact researchers here at UCSD drors glenner and Wong looked at Alzheimer's brains in the population when it was called scile dementia and they noted that it looked identical to Down syndrome tissue and they they published cases where they had
them side by side and it was impossible to tell the difference so the pathology is the same it appears that in the genetic forms of Alzheimer's disease there's an over production of beta ameloid whereas in the sporadic form of the disease which happens in the general population at an older age there's an there's an impaired clearance of beta ameloid out of the brain Mike what can we learn from people with Down Syndrome about Alzheimer's disease there's a lot to learn about Down syndrome as well as its relationship with Alzheimer's disease uh we have many research
studies ongoing right now to better understand the prevalence as well as the progression of Alzheimer's disease in people with Down Syndrome what's very interesting is that although all people with Down Syndrome by the age of 40 can have the plaques and Tangles not all of them show the signs of dementia and this is similar to in the general population where a third of people over the age of 65 that have no impairment whatsoever have the amalo plas and Tangles as well so why is there this dichotomy between having the pathological changes but not the symptoms
and we're very interested in understanding why is that and is there some Factor whether it's environmental genetic or other that is affecting the person's resilience and allows them to have cognitive uh abilities despite the presence of the plaques how do you study Alzheimer's disease and people with Down Syndrome how do you develop the knowledge base that allows you to make good guesses about pathogenesis one of the reasons that it's so exciting to be in the field of Alzheimer's disease today is that we're able to identify markers of the disease before patients really show symptoms and
we can correlate the accumulation of those various biomarkers and the changes in those biomarkers with clinical uh changes in patients uh for example we have a number of markers that allow us to visualize changes in the brain that occur in Alzheimer's disease in in people with Down Syndrome these include measurements of brain size and Regional areas within the brain and how they change with aging we look at amalo deposition in the brain amalo deposition in the retina amalo levels in the blood uh and it's not just amid we also look at tow deposition in the
brain as well as some other functional measures and cognitive measures in people with Down Syndrome that we believe are at high risk for developing Alzheimer's dementia down the road Mike you've been the author of a of a pilot study that aims to provide us with a natural history of these changes in people with Down Syndrome can you talk a little bit about that sure it it's been known for decades that people with Down Syndrome develop Alzheimer's disease pathology what hasn't been known is what is the rate of progression of those changes and is it happening
before the patients develop symptoms uh so we now have these non-invasive techniques uh that allow us to measure biomarker so the study that you're referring to is called the Down Syndrome biomarker initiative and this pilot study really looked at uh and looks at how patients with Down Syndrome or individuals with Down Syndrome uh can participate in a research study such as this are they capable and and what we have found so far is they are absolutely capable and they are eager to participate and they are U uh individuals that give full effort when they're participating
in research what we find is that the biomarker changes in people with Down Syndrome are identical to the changes we see on the same biomarkers and people with genetic forms of Alzheimer's disease so that's very exciting because it allows us to perhaps March even earlier in the course of the disease of Alzheimer's disease and find out when is the pathology really starting because we believe that may be the best time to intervene to maximize efficacy or benefit from any intervention are there plans to expand the study to include more people going forward the disb pilot
is a feasibility study for a much larger study and in fact last year we had a steering committee meeting with various members and organizations who are interested in this type of research our hope is to conduct a study with 200 individuals across multiple sites around the country to bring out uh this type of biomarker testing and understand the natural history of Alzheimer's disease and people with Down Syndrome so that potentially we can bring other developments in the field of Alzheimer's disease into this population as well and I would think that um if one really knows
that there's an evolution of this disorder in people with Down Syndrome what we learn in Down syndrome might well inform the markers we look for the things we measure in people with uh uh Alzheimer's disease due to other causes absolutely I think that uh the genetic populations including Down syndrome give us the opport opportunity to understand the earliest stages of where Alzheimer's disease may be starting and allow us to look at new non-invasive measures of Alzheimer's disease pathology what's unique about the Down Syndrome population is they represent the world's largest predetermined Alzheimer's disease population and
given the Baseline intellectual disability I believe they are the most vulnerable population to dementia therefore it makes the most sense to bring our latest advances in the world of Alzheimer's disease to this population that is number one genetically predetermined and number two more vulnerable so there's a dream uh that one day hopefully soon will'll know enough about Alzheimer's disease and down syndrome that we might actually prevent Alzheimer's disease in everybody absolutely and secondary prevention means that you understand there's a positive biomarker in an individual before they develop any symptoms and we would love to bring
the latest therapies that are being looked at in the general population as well as the other genetic forms of Alzheimer's disease into the Down Syndrome population and perhaps glean better understanding of when is the right time to intervene to have secondary prevention in Alzheimer's disease exciting uh what trials are you uh involved in right now at UCSD Mike there are multiple studies that we're conducting at our site one is a behavioral intervention where we observe uh participation in a weekly yoga session [Music] brought into the clinic for testing all exciting stuff is there anything on
the horizon that you'd like to talk about well we've just been awarded an IH Grant to conduct an anti- ameloid study in individuals with Down syndrome and I think this is really leveraging all of the interest in Alzheimer's disease and in that field in terms of secondary prevention and bringing it into a population that I think would inform us the Alzheimer's World about when is the best time to intervene and also bring the latest technology and treatment into this population great what would you advise a family with a loved one with Down Syndrome who's an
adult uh with respect to what they might do to become more involved in this process I think that it's very important to keep in mind that clinicians are there to provide assessments of how a patient is doing in a snapshot of time what's most helpful is to have the individual followed over time so that we know if the changes are um behavioral Psy ological or truly a neurodegenerative disease I would encourage all family members to have uh the individual with Down Syndrome evaluated by their clinician to obtain Baseline testing so that if there is a
change they would they would be able to act accordingly certainly participating in research is another way to get access to uh more assessments of that individual and and I think we can encourage All Families of people with Down Syndrome to be aware of what's going on in the world the new research that's happening and and to make themselves available for research activities that uh help them but also help others with Down Syndrome Mike thanks for being with me for Bill Mobley and uh the honor mind series uh thanks for being with [Music] us [Music] [Music]
