As I am away at school and my grandparents get older and
older, I often find myself worrying about their health and overall well-being. Will there ever be a time when I come home
and they no longer recognize me? The
thought of this is very frightening. Much information regarding Alzheimer’s disease
(AD) remains unknown. Although Alzheimer’s
has not personally affected anyone close to me, 40 million people worldwide are
currently suffering from this incurable disease. I cannot imagine how heartbreaking it must be
to watch the memory of a loved one progressively deteriorate. Unfortunately there are still no reliable
cures, effective therapies, and early diagnostic methods available that
indicate AD before it has already progressed to major memory loss.
Biomarkers,
which are simply characteristics that are measured and evaluated as an
indicator of normal biological processes, pathogenic processes or
pharmacological responses to a therapeutic intervention, remain few and far between. Current biomarkers including
cerebrospinal fluid, proteins such as tau and amyloid-β, and MRI are invasive,
time-consuming, and expensive.
Researchers have discovered a possible alternative that involves
measuring the membrane proteins in red blood cells (RBC). In a recent study, scientists analyzed the
changes in the expression levels of numerous RBC membrane proteins in patients
diagnosed with both late and early onset AD.
The proteins were chosen based on bioinformatics and analysis of
genome-wide association studies, Online Mendelian Inheritance in Man, and red
blood cell databases.
The
experiment was conducted by selecting forty patients who had been diagnosed
with Alzheimer’s disease. Twenty-seven
of these patients were classified with late onset AD (ages >70) and thirteen
were characterized by having early onset AD (age <61). Researchers used a method known as flow
cytometry in order to perform RBC membrane protein determinations. Put simply, flow cytometry is a technique
used to analyze the physical and chemical characteristics of particles (in this
case RBC) as they pass through at least one laser. This study quantitated the red cell membrane
protein levels of the following: GLUT1,
ABCA1, ABCG2, INSR (insulin receptor), and PMACA4b.
The data
showed a significant increase in the expression of GLUT1 in both late and early
onset AD patients. From this information,
researchers hypothesized that this increase reflects an upregulation of this
transporter in the blood-brain barrier endothelial cells, caused by starvation
and/or lack of oxygen in the tissues of the brain. Similar results were found in INSR. A significant increase in INSR in both late
and early onset AD patients may also reflect an upregulation in RBC-INSR
expression, which could be caused by insulin deficiency in the central nervous
system. Increased expression was also
found in both ABCA1 and ABCG2. Increased
ABCA1 could reflect a long-term regulatory response in cholesterol
transport. Furthermore, ABCG2, which is
known to protect the CNS from amyloid (a starch-like protein) accumulation, was hypothesized to be upregulated due to its higher expression as well.
The
increased expression of these proteins in red blood cell membranes of patients
with Alzheimer’s disease is thought to indicate underlying metabolic changes as
well as upregulation of these proteins in tissues associated with the CNS. This
in turn may have transcriptional and translational effects.
Obviously
further research must be conducted in this area but this seems to be a substantial
foundation. Narrowing down the
indicators of Alzheimer’s is a step in the direction of discovering a cure. There is still a long way to go but I hope
this proposal of using proteins on red blood cell membranes can be one of the
tools necessary for the construction of preventative methods of this
disease. No one should have to suffer
from a disease that takes away the memories of a lifetime.
Works Cited:
Várady, György, Edit Szabó, Ágnes Fehér, Adrienn Németh,
Boglárka Zámbó, Magdolna Pákáski,
Zoltán Janka, and Balázs Sarkadi. "Alterations of Membrane Protein Expression in Red Blood Cells
Of Alzheimer's Disease Patients." Alzheimer's & Dementia: Diagnosis, Assessment &
Disease Monitoring 1.3 (2015): 334-38. ScienceDirect.
Web. 11 Oct. 2015.
"What Is a Biomarker?" News-Medical.net. News
Medical Life Sciences & Medicine, 1 June
2010. Web. 11 Oct. 2015.
"What Is Flow Cytometry?" News-Medical.net.
News Medical Life Sciences & Medicine,
11 May 2010. Web. 11 Oct. 2015.
Image citation:
"Alzheimer's Brain." Wikimedia Commons. 13 Oct.
2011. Web.
In this study, patients were already experiencing signs of Alzheimer's Disease. I wonder what levels of increases in the expression of GLUT1, INSR, ABCA1 and ABCG2 would be indicative of developing Alzheimer's. If we can determine the circumstances involved in development of the disease, it may shed some light on the causes as well. I wonder, too, if the changes in regulation could be influenced by environmental toxins.
ReplyDeleteHi Nicole! Natalie spoke to the comment I was going to make - the real question is finding a biomarker that will show in the prodromal phase of Alzheimer's since interventions offered after overt signs do not work well. The key is to find the marker(s) early and then administering (something) that will help to prevent further problems. I'm working with a group now to try to find these markers in an animal model. This work in humans is quite promising.
ReplyDeleteShould there be annual testing using biomarkers for senior citizens in order to catch the disease early? I agree with Natalie and Dr. Deruisseau in that these patients were already diagnosed with Alzheimer’s disease – it would be interesting to see if patient who were developing Alzheimer’s disease could be studied and see what changes are occurring in their brain function in order to determine what is causing it. I wonder if all the red cell membrane proteins (GLUT1, ABCA1, ABCG2, INSR, and PMACA4b) all contribute to Alzheimer’s disease or just one. What exactly happens to the brain? The image shows severe deterioration. What level of protein expression in the red blood cell membrane is indicative of Alzheimer’s? I know a lot of people who have had loved ones suffer from this disease and it is truly heartbreaking. More research should be conducted in order to find a proper biomarker that will indicate a person is developing this disease, which can ultimately lead to discovering what causes it.
ReplyDeleteAlzheimer's is a terrible disease. I have seen the way it affects people, such as my aunt, and the progression is heartbreaking. It saddens me to know that such horrible diseases can just ravage a body/brain and there is just no stopping it. However, it is very interesting that scientists can identity markers of the disease. This is an obvious step in the right direction. Steps like these will continue to lead doctors in the correct direction in learning more about causes, treatments and potential cures.The underlying metabolic changes seems to be important in the identification of AD. This is a disease that is very difficult to live with and live around. I really truly hope that studies like these will continue and preventative measures will eventually be developed.
ReplyDeleteOne thing I wasn't clear on: what are ABCA and ABCG? I noticed that you said the researchers found that ABCG works to protect against beta amyloid accumulation. I'm wondering if it is a degradation type of protein or if it is something like a caperonin? I think it is definitely something to look more into. If this ABCG turns out to be a degradation protein, then geneticists could work to recreate it in laboratory setting. Wouldn't it be awesome if they could make a treatment that just totally breaks down the plaques that form on neurons?
ReplyDeleteIn this article, it is stated that there was an increased amount of GLUT1 due to the starvation and/or lack of oxygen in the tissues of the brain. Did you encounter any of the reasons behind why these tissues may have a deprivation of oxygen? Also, I wonder what other implications or effects this lack of oxygen has on the tissues of the brain. If the blood brain barrier of the endothelial cells expresses abnormal levels of these proteins, I wonder if somehow these levels could be used as a screening for the development of Alzheimer’s. This area of research has so much potential in the future and it is great to see advances being made!
ReplyDeleteThis article was very interesting to me. While I have never experienced Alzheimer's disease first hand, hearing stories of the disease allow me to at least somewhat understand some of the affects that it causes. I wonder if this form of testing red cell membrane proteins can be or has been used for other types of neurodegenerative diseases as well. It would be interesting to see if the same proteins were elevated in other diseases or if they would vary. Either way, this research is very promising at least in terms of future research in preventative treatment for Alzheimer's disease as well as other types of neurodegenerative diseases.
ReplyDeleteThere has been heavy research in regards to Alzheimer's disease over the past few decades and that is crucial for developing new treatments for patients with this disease. I'm also just curious to what specific levels of expression of GLUT1, INSR, and ABCA1 would predispose the development of Alzheimer's. That's crucial to note in terms of understanding the causation in this disease. I had no idea about the importance of biomarkers and how crucial they are to detect early and then direct that will help to prevent further complications. Overall, a very interesting read especially in the hope of developing further treatments for Alzheimer's patients in the coming years.
ReplyDeleteAn interesting follow up study could include testing many people with Alzheimer's risk before the onset of the disease progressively as they go into old age and record their RBC receptor levels. Then if some of the members of the study do develop the disease, their recorded RBC receptor levels from the previous years could be compared to those who did not develop the condition, and this may reveal a way to diagnose this problem early. While an early diagnosis would only be somewhat helpful as there are little treatments, if will be immensely valuable once effective treatments are created. Hopefully research progresses swiftly, as Alzheimer's is the 6th leading cause of death in the United States.
ReplyDeleteAn interesting follow up study could include testing many people with Alzheimer's risk before the onset of the disease progressively as they go into old age and record their RBC receptor levels. Then if some of the members of the study do develop the disease, their recorded RBC receptor levels from the previous years could be compared to those who did not develop the condition, and this may reveal a way to diagnose this problem early. While an early diagnosis would only be somewhat helpful as there are little treatments, if will be immensely valuable once effective treatments are created. Hopefully research progresses swiftly, as Alzheimer's is the 6th leading cause of death in the United States.
ReplyDeleteAlzheimer's is a disease that not only largely impacts the person with the disease but also their family. Many family members who have a relative that has Alzheimer's disease are afraid of inheriting the disease themselves. However, 50% of people who have acquired a late onset of Alzheimer's do not have any known relatives that had this disease.Researchers should observe not just people who have been diagnosed with Alzheimer's but also the elderly that do not have Alzheimer's. They should compare and contrast the differences of their RBC receptor levels.
ReplyDeleteAlzheimer's is a disease that not only largely impacts the person with the disease but also their family. Many family members who have a relative that has Alzheimer's disease are afraid of inheriting the disease themselves. However, 50% of people who have acquired a late onset of Alzheimer's do not have any known relatives that had this disease.Researchers should observe not just people who have been diagnosed with Alzheimer's but also the elderly that do not have Alzheimer's. They should compare and contrast the differences of their RBC receptor levels.
ReplyDeleteIt is sad that so many people suffer from this disease. This is interesting research that they may be able to detect Alzheimer's with certain increases in proteins based on RBC's. It would be amazing to not have to run such expensive tests such as MRI's to diagnose this disease. I think the research would be more profound if they tested these protein levels on younger people who may not have any precursors to Alzheimer's as well as people in their 40's and 50's to see when these protein levels begin to change and increase and how this may lead to the brain changes and Alzheimer's. With this research and learning more about the proteins and their function how can we use this to take preventative measures or learn how to effectively treat Alzheimer's?
ReplyDeleteMy grandfather lived with Alzheimer's Disease for over 10 years, with the disease stealing away all his memories and ability to function through day to day tasks. I suppose you could characterize his as early onset because he was fist diagnosed in his early 60's, although I am not certain of the exact year. Now, as my own father is getting older, there is most definitely fear that he may share the same fate his father did. I was very intrigued reading the findings of the research in this study, wondering if these metabolic changes/upregulation of proteins come from a genetic background, or if it is driven more by the environment that the person lives in. I suppose, as mentioned above, that the person would be more susceptible to these factors if their brain was more starved for oxygen. I find myself wondering what causes this starvation of oxygen, and once again, if this starvation is something that some people will naturally experience due to their genetics, or if it more environmentally derived. If this lack of oxygen is something that can be prevented, I wonder if it would be possible to somehow test for these levels starting at a certain age before actual symptoms set in. I feel that by the time the symptoms set in, it would be too late to "cure" the deterioration in the brain, and therefore seeking out preventative measures is more useful and time worthy.
ReplyDeleteI have worked with a couple of patients with AD and it is very sad to see them get very frustrated when they keep forgetting things. With 40 million people world wide having this disease it is very important that we work on finding a cure for it. Could the answer to how this disease can be cured be found in the human genome project? I am also very curious if maybe part of the problem could endocrine disruption. In the article you said that the researchers hypothesized that it could be from insulin deficiency and a cholesterol transport problem and both of these make me think that it could partially be caused by environmental endocrine disrupting chemicals. Looking into the insulin deficiency would be an interesting follow up study I think.
ReplyDelete