From Medscape Medical News
Biomarkers Appear to Predict Alzheimer's Disease
Allison Gandey
July 27, 2009 ? Several cerebrospinal-fluid biomarkers have shown accuracy in identifying patients with mild cognitive impairment who went on to develop Alzheimer's disease (AD). The new results, from a multicenter study, appear in the July 22 issue of the Journal of the American Medical Association.
"The study clearly verifies that the cerebrospinal-fluid biomarkers beta-amyloid 42 (A?42), T-tau, and P-tau may identify early-stage Alzheimer's disease," lead investigator Niklas Mattsson, MD, from Sahlgrenska University, in M?lndal, Sweden, told Medscape Neurology. "This is highly important, since the deleterious disease process is well under way long before symptoms progress to dementia. Disease-modifying intervention must be initiated at the earliest possible stage before too much damage has been inflicted on the brain."
In an accompanying editorial, Ronald Petersen, PhD, MD, from the Mayo Clinic Study of Aging, in Rochester, Minnesota, and John Trojanowski, MD, PhD, from the University of Pennsylvania School of Medicine, in Philadelphia, suggest that this study represents "a major step forward".
Cerebrospinal-Fluid Biomarkers Show Promise
The study had 2 parts ? a cross-sectional component and a prospective evaluation. The cross-sectional phase of the study identified biomarker cutoff levels in patients with AD and controls. The prospective phase evaluated patients with cognitive impairment from 12 centers in the United States and Europe.
There were 750 patients with mild cognitive impairment, 529 with AD, and 304 controls. Researchers followed patients with mild cognitive impairment for at least 2 years or until symptoms had progressed to clinical dementia.
During follow-up, 271 patients were diagnosed with AD and 59 were diagnosed with other dementias.
The researchers found that the A?42 assay had considerable intersite variability. Patients who developed AD had lower median levels of A?42, higher levels of tau phosphorylated at position threonine, and higher total tau protein levels than patients who did not develop AD during follow-up.
"The data likely reflect the underlying pathological processes of Alzheimer's disease in some individuals with mild cognitive impairment," write Drs. Petersen and Trojanowski. "However, it is premature to recommend application of these techniques in clinical practice."
They add that the report highlights the challenges but also suggests solutions. "Subsequent prospective investigations should clarify the true utility of these measures."
Senior author Kaj Blennow, MD, PhD, from the Sahlgrenska Academy at University of Gothenburg, in M?lndal, Sweden, reports receiving a consulting fee for an advisory board meeting from Innogenetics. The other study authors have disclosed no relevant financial relationships. Editorialist Dr. Petersen reports serving as chair of the safety-monitoring committee and as a consultant for Elan Pharmaceuticals. He was also chair of the data-monitoring committee for Wyeth Pharmaceuticals and a consultant for GE Healthcare.
JAMA. 2009;302:385-393 and 436-437. Abstract, Abstract
Biomarkers Appear to Predict Alzheimer's Disease
Allison Gandey
July 27, 2009 ? Several cerebrospinal-fluid biomarkers have shown accuracy in identifying patients with mild cognitive impairment who went on to develop Alzheimer's disease (AD). The new results, from a multicenter study, appear in the July 22 issue of the Journal of the American Medical Association.
"The study clearly verifies that the cerebrospinal-fluid biomarkers beta-amyloid 42 (A?42), T-tau, and P-tau may identify early-stage Alzheimer's disease," lead investigator Niklas Mattsson, MD, from Sahlgrenska University, in M?lndal, Sweden, told Medscape Neurology. "This is highly important, since the deleterious disease process is well under way long before symptoms progress to dementia. Disease-modifying intervention must be initiated at the earliest possible stage before too much damage has been inflicted on the brain."
In an accompanying editorial, Ronald Petersen, PhD, MD, from the Mayo Clinic Study of Aging, in Rochester, Minnesota, and John Trojanowski, MD, PhD, from the University of Pennsylvania School of Medicine, in Philadelphia, suggest that this study represents "a major step forward".
Cerebrospinal-Fluid Biomarkers Show Promise
The study had 2 parts ? a cross-sectional component and a prospective evaluation. The cross-sectional phase of the study identified biomarker cutoff levels in patients with AD and controls. The prospective phase evaluated patients with cognitive impairment from 12 centers in the United States and Europe.
There were 750 patients with mild cognitive impairment, 529 with AD, and 304 controls. Researchers followed patients with mild cognitive impairment for at least 2 years or until symptoms had progressed to clinical dementia.
During follow-up, 271 patients were diagnosed with AD and 59 were diagnosed with other dementias.
The researchers found that the A?42 assay had considerable intersite variability. Patients who developed AD had lower median levels of A?42, higher levels of tau phosphorylated at position threonine, and higher total tau protein levels than patients who did not develop AD during follow-up.
"The data likely reflect the underlying pathological processes of Alzheimer's disease in some individuals with mild cognitive impairment," write Drs. Petersen and Trojanowski. "However, it is premature to recommend application of these techniques in clinical practice."
They add that the report highlights the challenges but also suggests solutions. "Subsequent prospective investigations should clarify the true utility of these measures."
Senior author Kaj Blennow, MD, PhD, from the Sahlgrenska Academy at University of Gothenburg, in M?lndal, Sweden, reports receiving a consulting fee for an advisory board meeting from Innogenetics. The other study authors have disclosed no relevant financial relationships. Editorialist Dr. Petersen reports serving as chair of the safety-monitoring committee and as a consultant for Elan Pharmaceuticals. He was also chair of the data-monitoring committee for Wyeth Pharmaceuticals and a consultant for GE Healthcare.
JAMA. 2009;302:385-393 and 436-437. Abstract, Abstract
