What are STEP proteins? [ 12/03/10 ]
STEP is an acronym used for convenience and refers to "STriatal-Enriched tyrosine Phosphatase," a protein associated with the regulation of learning and memory. In mice with a condition similar to Alzheimer's disease, lowering the level of STEP reversed cognitive deficits. A current leader in work on STEP, Dr. Paul Lombroso at Yale School of Medicine, has stated that beta amyloid activates STEP, which in turn interferes with glutamatergic neurotransmission*, and that this effect may be an important contributor to impaired learning and memory in Alzheimer's disease. Increase levels of STEP may contribute to the problems seen in other diseases as well, such as schizophrenia and Fragile X syndrome. Current research is evaluating the treatment implications of findings relating STEP to cognitive impairment.
*Glutamatergic neurotransmission: nerve cells that communicate with one another using the glutamate molecule.
My 78-year-old husband is extremely well educated and speaks 6 languages, but has all the classic symptoms of Alzheimer’s disease. He needs help with all daily living activities and cannot remember anything. I am limiting his driving to daytime and only to places that he is familiar with, such as the grocery store and church. Soon, however, he will need to stop driving entirely. His doctor gave him a 5 minute test and said that he does not have Alzheimer’s disease. Why is it so hard to get a diagnosis for this disease? [ 12/02/10 ]
Your husband should be evaluated thoroughly by a behavioral neurologist or a neuropsychiatrist, if available, since they are familiar with the brain conditions that affect behavior, and more extensive testing should be done. An intelligent, highly educated individual may perform well on the simplified cognitive screening tests that are sometimes done in primary care settings, yielding a misleading impression that dementia is not present. On the other hand, dementia is not the only condition that can result in forgetfulness. Alzheimer's disease is the most common dementia, but not the only one, so if your husband does have dementia it is still valuable to refine the diagnosis in an effort to individualize his treatment. Finally, I'd advise that he stop driving right away pending further assessment. Although a significantly cognitively impaired individual may retain the capacity to drive safely under optimal conditions, something as routine as a child running in front of the car might result in confusion and impaired reaction, resulting in a tragic outcome.
My wife has had amyloid deposits surgically removed from her eyes, and it is the only such condition that her eye doctor has ever seen. The biopsy was sent to an expert in Atlanta, and he had never seen this condition before either. Was the amyloid that was removed from her eyes a precursor to Alzheimer’s disease? [ 12/01/10 ]
Although I do not know the details of your wife's ophthalmologic problems, ocular accumulation of beta amyloid is well recognized. Glaucoma or cataracts may be early complications of this process. Beta amyloid accumulation occurs not only in Alzheimer's disease but also in Down's syndrome, another condition in which beta amyloid can accumulate (resulting in early-onset dementia). The possibility of detecting Alzheimer's disease at an earlier stage through ocular examination has been raised and you may wish to read more about it (see for example the review by Frost and colleagues in the Journal of Alzheimer's Disease, 2010, 22:1-16). They emphasize that the eye is connected by nerves to the brain and that the eye is a unique site for observing vasculature and neural tissue non-invasively. Whether your wife's condition is a forerunner to the development of Alzheimer's disease later in life is not clear, but she should certainly be followed by ophthalmologists who can help her avoid damage to her vision.
For more information concerning the technology to examine ocular beta amyloid, please read about the research of Dr. Lee Goldstein, which is funded by our organization.
I have read that amino acids can help a person who has Alzheimer’s disease. Please let me know if you have any information on this topic. [ 11/30/10 ]
Amino acids are simple molecules that serve as the building blocks of proteins. Since proteins are necessary for many biological processes, we need to have these amino acids available. Most can be produced within our own bodies, though some are obtained only through dietary means. A diet with adequate protein intake should not lead to amino acid deficiency in a healthy individual, and there is no solid evidence currently that extra supplementation with amino acids alone is helpful in preventing or treating Alzheimer's disease.
Why does amyloid beta aggregate into plaques and fibrils? What exactly is involved in the process of amyloid beta forming monomers, dimers, trimers, oligomers, protofibrils, fibrils, and eventually plaques? I'm really interested into the biochemistry of amyloid beta in pathogenesis of Alzheimer's disease. [ 11/30/10 ]
Amyloid beta is a protein, which means it's a string of amino acids linked through chemical bonds. The fibrils result when peptide strands bind together as a result of the molecular characteristics of the amino acids. Amyloid plaques are sheets of the fibrils bound together as a result of electrostatic and chemical bonding. The precise mechanism through which amyloid causes Alzheimer's disease (if indeed it does) remains unclear, but likely involves interference with synaptic transmission as well as instigation of neuron-killing local inflammatory reactions.
I am 56 years old and have had a grand mal seizure disorder since I was 35. As long as I take my medication I have no seizures. Before having seizures I had an excellent memory; however, I was informed recently that I have Alzheimer’s disease. Is there any correlation between seizures and the development of dementia or Alzheimer’s disease? [ 11/03/10 ]
Although seizures are not thought to lead to Alzheimer's disease, there are a variety of ways in which seizures are associated with dementia. A seizure in progress interrupts the process of memory formation so that no new memories are made during the seizure and some memories from just before the seizure are not stored. Seizures can cause excessive excitement of brain cells resulting in a destructive effect that damages memory. Seizures that lead to hypoxia (a period of insufficient oxygen levels) or head injury can be even more damaging to the brain. Some of the medications that treat epilepsy produce sedation or forgetfulness in some patients. Furthermore, there are medical conditions (such as brain injury) that can result in both seizures and dementia. Finally, seizures can develop in people affected by Alzheimer's disease although this is not a common occurrence. You are young for the onset of Alzheimer's disease, so if you have experienced epilepsy and memory loss and been told that you have Alzheimer's disease, I hope you will make sure that a physician skilled in the diagnosis and management of dementia confirms this diagnosis.
My grandmother, her sister and my aunt have died from Alzheimer’s disease. My mother was diagnosed 6 years ago and is now in the final stages of the disease. My sister and I have watched my mother succumb to this disorder with great concern and worry if we also are at risk. I do understand the benefits of medications such as Aricept, and wonder if this class of medications could prevent the onset of the disease if they were used prior to the onset of symptoms? If so, how do I encourage my doctor to write a prescription? Right now, he says that as long as I have no symptoms, I shouldn't worry. [ 11/02/10 ]
Your concern is understandable, since it must have been exceedingly difficult to witness the illnesses of your grandmother and her sister, your aunt, and your mother. Indeed you and your sister are at greater risk than individuals without so many affected relatives. If the onset of your relatives' illness was early, the risk is greater. Still, it's very important to realize that many older adults with affected close relatives never develop Alzheimer's disease. The cognitive enhancing medications such as Aricept (donepezil) and others have not been shown to prevent the onset of the disease when used prior to symptom onset. In fact, there is nothing at this time that has definitively been shown to prevent Alzheimer's disease or other dementias; however, there is preliminary data to support the benefit of some interventions, such as physical activity and cardiovascular risk reduction. Please seek evaluation if symptoms of cognitive change are noticed by you or your sister.
Can you tell me more about the blood test that was recently discovered to help detect frontotemporal dementia (FTD)? I want to be armed with the correct information prior to going back to see my physician. Are some doctors currently using this test to help diagnose FTD? [ 11/01/10 ]
Dr. Kristel Sleegers and colleagues at the Flanders Insititue for Biotechnology and elsewhere published in 2009 (Ann Neurol 65:603-9) their results on a blood test that uses levels of progranulin to distinguish individuals carrying specific gene mutations that result in certain types of frontotemporal dementia from individuals who were not carrying those genes. This was an important research finding but not one yet ready for clinical use for the following reasons:
- Not all individuals with FTD would be detected by this blood test.
- Some individuals who would be identified as pre-symptomatic but at risk genetically for developing FTD would not actually develop symptoms until late in life.
- It is not certain yet that a "positive" result on this test would identify FTD accurately if certain other neurodegenerative diseases were present.
- Since there is no specific treatment for the type of FTD identified by this test it is not clear that those at genetic risk should be identified except perhaps for research purposes.
This research nonetheless advanced our understanding of FTD by demonstrating functional deficiency of the serum protein progranulin in both clinically affected and unaffected individuals carrying genes known to be associated with individuals affected by or at risk for a certain class of FTD.