Alzheimer’s disease is the most common cause of dementia. It is different from other causes of cognitive impairment and dementia because it is defined by the abundance of the two hallmark deposits found in the brains of patients with Alzheimer’s disease: neurofibrillary tangles formed by tau amyloid fibrils and senile plaques formed by beta amyloid (Aβ) fibrils. It causes progressive loss of intellectual and social skills severe enough to interfere with day-to-day life. The brain cells degenerate and die due to the damaging effects of the tangles and plaques thereby causing a steady decline in memory and mental function. Current medications and management strategies can temporarily improve Alzheimer’s symptoms, maximize function and maintain independence.
Researchers at Penn are involved in several studies designed to develop an easy test that can find the disease early on. With an easy and accurate diagnosis in the early stages of development, doctors can gain a better understanding of Alzheimer’s disease and look at more effective treatments for this disease.
Searching for Biomarkers
For more than 20 years, Penn researchers have investigated methods for diagnosing Alzheimer’s disease. Early success came from the development of a radioactive tracer that could detect the beta amyloid plaques associated with Alzheimer’s in the brain. The tell-tale chemical and physical indicators of the changes in the brain are known as “biomarkers.” Studies under way in Penn’s Alzheimer’s Disease Core Center use and compare different diagnostic technologies to detect these biomarkers of changes in the brain.
Penn researchers identify, measure and store the specific biomarkers found in proteins and fluids to better understand the physiological changes that occur over time in Alzheimer’s disease. “We look for consistency in these tests so that we can accurately interpret these biomarkers,” said John Q. Trojanowski, MD, PhD, co-director of Penn’s Center for Neurodegenerative Disease Research and director of the Alzheimer’s Disease Core Center. “We are close to being able to predict which patients will develop cognitive disease.”
Cerebrospinal Fluid Sampling
Cerebrospinal fluid (CSF) is the fluid that circulates through the brain and the spinal cord. It acts as a “shock absorber” for protection of these areas and contains proteins and other important biomarkers that may indicate existence of diseases such as Alzheimer’s. By analyzing CSF, Penn researchers can pinpoint the biomarkers that may signal an increased risk of developing disease. The CSF is obtained through a simple and safe process known as a lumbar puncture or spinal tap. The procedure is quick and involves no, or only slight discomfort.
Neuroimaging
Neuroimaging studies compare different diagnostic technologies to detect changes in the brains of patients with Alzheimer’s. PET scanners look at how the various brain regions use glucose. Doctors can tell by the pattern of glucose use whether a brain is developing Alzheimer’s because nerve cells use less glucose when they are beginning to fail. But PET can be expensive and the radioactive tracers used to create the images carry some risks for patient needing repeated testing.
New Penn Medicine studies examining MRI imaging of blood flow in each brain region mirrors the glucose use seen in the PET scans. The studies, published in November 2011 in Alzheimer’s and Dementia and Neurology, show MRI may be a useful way of diagnosing the disease and managing therapy. “This can become a useful way of diagnosing the disease and managing therapy,” said study co-author John Detre, MD, Penn neurologist.
Dr. Trojanowski and Leslie Shaw, PhD, also co-lead the Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a public-private partnership launched in 2004 at 58 sites in the U.S. and Canada. Several hundred investigators are following more than 1,000 subjects over time to assess how the biomarkers change to reflect the onset and progression of cognitive impairment and dementia. The partnership extends through 2016 and is funded by grant support from the National Institute on Aging, pharmaceutical companies and foundations to identify, standardize and validate informative biomarkers for Alzheimer’s disease.
Biomarker for Tau-Related Brain Disorders
Penn researchers led by Virginia M.-Y. Lee, PhD, MBA, recently determined that a well-known chemical process called acetylation is associated with one of the biological processes related to Alzheimer’s disease and related disorders, and they seek to exploit this finding in their biomarker and drug discovery research in the near future.
Tau is one of the primary disease proteins associated with neurodegenerative diseases including Alzheimer’s. Tau proteins are expressed primarily in the central nervous system where they help with the assembly and stability of microtubules, the protein structures that are the backbone of the nerve-cell communication system.
“Cerebrospinal fluid sampling can measure these tau proteins that are the building block proteins of Alzheimer’s disease tangles, which correlate with the severity of the disease at autopsy. The hope is that by measuring tau in CSF, one can diagnose Alzheimer’s disease with more certainty during life. Indeed, our bold, long-term goal is to convert the current ‘gold standard’ for the definite diagnosis of Alzheimer’s disease. We hope to move from an autopsy evaluation to one that is done with living patients early in the disease process by developing a new biomarker standard for the definite diagnosis of Alzheimer’s disease and using a panel of biomarkers that includes measuring the levels of CSF tau,” said Dr. Trojanowksi. “Patients with Alzheimer’s and other dementias have an increased level of neurofibrillary tangles made up of tau proteins. By understanding the role of plaques and tangles we move closer to understanding and treating Alzheimer’s disease.”
For more information, or to schedule an appointment visit PennMedicine.org or call 800-789-PENN (7366).
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