There was interesting news yesterday out of UPenn. Researchers tested cerebrospinal fluid (CSF) for concentrations of amyloid beta42 peptide and tau protein. The test "was 87 percent accurate at predicting which patients with early memory problems and other symptoms of cognitive impairment would eventually be diagnosed with Alzheimer's," according to a Reuters news story. This test might be helpful in LBD as LBD usually co-occurs with Alzheimer's Disease.
This release is available online at
http://www.uphs.upenn.edu/news/News_Rel ... arker.html
I couldn't find the abstract of the Annals of Neurology article either on that journal's website or PubMed. There are some related articles in the journal Neuroimaging that have abstracts available on PubMed. I guess we'll have to be satisfied with the press release for now.
March 16, 2009
UPenn Press Release
Penn Medicine Pathologists Pioneer Biomarker Test to Diagnose or Rule Out Alzheimerâs Disease
Biomarker Signatures Predict Conversion from Mild Cognitive Impairment to Alzheimerâs Disease
PHILADELPHIA, PA Â A test capable of confirming or ruling out Alzheimerâs disease has been validated and standardized by researchers at the University of Pennsylvania School of Medicine. By measuring cerebrospinal fluid (CSF) concentrations of two of the diseaseâs biochemical hallmarks Â amyloid beta42 peptide and tau protein Â the test also predicted whether a personâs mild cognitive impairment would convert to Alzheimerâs disease over time. Researchers were able to detect this devastating disease at the earliest stages, before dementia symptoms appeared and widespread irreversible damage occurred. The findings hold promise in the search for effective pharmaceutical therapies capable of halting the disease.
Homing in on a previously suggested pathological CSF biomarker signature, a team of Penn Medicine researchers, led by Leslie M. Shaw, PhD, Co-Director of the Penn Alzheimerâs Disease Neuroimaging Initiative (ADNI) Biomarker Core, found evidence of neuron degeneration Â marked by an increase in CSF concentration of tau proteins Â and plaque deposition, indicated by a decrease in amyloid beta42 concentration. In addition, people with two copies of the genetic risk factor for Alzheimerâs disease, APOE e4 , had the lowest concentrations of amyloid beta42, compared to those with one or no copies. The study appears in the online edition of the Annals of Neurology.
âWith this test, we can reliably detect and track the progression of Alzheimerâs disease,â said Dr. Shaw. âValidated biomarker tests will improve the focus of Alzheimerâs clinical trials, enrolling patients at earlier stages of the disease to find treatments that can at least delay Âand perhaps stopÂ neurodegeneration. In addition, prevention trials can test methods to delay or block mild cognitive impairment from converting to full-blown Alzheimerâs.â
Further validation studies of this research test system are underway. Additional work is needed to develop additional biomarkers, as well as identify more genetic risk factors that will help distinguish Alzheimerâs from other neurodegenerative diseases characterized by cognitive impairments.
âThanks to the dedicated researchers and volunteers who participated in this and other Alzheimerâs disease studies through the Penn Alzheimerâs Disease Core Center and at ADNI trial sites around the US and Canada, we have validated a test where a safe, simple lumbar puncture can provide information to confirm suspected Alzheimerâs disease and predict the onset of the disease,â said John Q. Trojanowski, MD, PhD, Director of the Penn Alzheimerâs Disease Core Center. âUsing this technique, we will further our understanding of how the disease progresses and what we can do to stop Alzheimerâs disease before it starts.â
About the Study
Cerebral spinal fluid samples contributed by 410 ADNI volunteers at 56 sites across the U.S. and Canada were included in this study. To independently establish threshold values for these biomarkers, cerebrospinal fluid samples from 52 Penn Memory Center volunteers with normal cognition and 56 people with confirmed Alzheimerâs disease based on post-mortem autopsy diagnosis were also measured. The test was based on the multiplexed xMAP microbead immunoassay system, with reagents provided by Innogenetics.
When compared with normal, healthy adults of the same age, a pattern of changes emerged in people with mild cognitive impairment or Alzheimerâs disease. In this group, tau concentrations increased, while amyloid beta42 levels decreased as the disease progressed.
* The test was 87 percent accurate overall (80 percent or above is considered clinically useful).
o In the CSF samples from those with autopsy-confirmed Alzheimerâs disease, the amyloid beta42 concentration threshold was
most sensitive and detected Alzheimerâs disease at a rate of 96.4 percent.
o The test accurately ruled out Alzheimerâs disease in 95.2 percent of the subjects.
o The test positively predicted the conversion from mild cognitive impairment to Alzheimerâs disease at a rate of 81.8 percent.
Data used in preparing this article were produced by the Alzheimerâs Disease Neuroimaging Initiative (ADNI) Biomarker Core at Penn or obtained from the ADNI database (www.loni.ucla.edu/ADNI
). Many ADNI investigators contributed to the design and implementation of ADNI or provided information but did not participate in the analysis of the data presented here or in the writing of this report. A complete list of ANDI investigators is available at http://www.loni.ucla.edu/ADNI/Collabora ... p_list.pdf
The ADNI public-private partnership includes federal support from the National Institute on Aging and the National Institute for Biomedical Imaging and Bioengineering, both part of the National Institutes of Health, and the participation of the Food and Drug Administration. Private sector support comes from pharmaceutical companies and other organizations through the Foundation for NIH, which has raised more than $25 million from both corporations and non-profits toward ADNI. Current private sector funders include Abbott Laboratories, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, General Electric Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Inc., Merck & Co., Inc., Novartis AG, Pfizer Inc, F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., and Wyeth Research, as well as non-profit partners the Alzheimerâs Association and the Institute for the Study of Aging.
PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nationâs top ten âHonor Rollâ hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.