 |
|
Cerebrospinal Fluid Levels of β-Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer Dementia
Peder Buchhave, MD, PhD;
Lennart Minthon, MD, PhD;
Henrik Zetterberg, MD, PhD;
Åsa K. Wallin, MD, PhD;
Kaj Blennow, MD, PhD;
Oskar Hansson, MD, PhD
Arch Gen Psychiatry. 2012;69(1):98-106. doi:10.1001/archgenpsychiatry.2011.155
Context Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease.
Objectives To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD.
Design A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years).
Setting Memory disorder clinic.
Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline.
Main Outcome Measure Conversion to AD dementia.
Results During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%.
Conclusions Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.
Author Affiliations: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö (Drs Buchhave, Minthon, Wallin, and Hansson); Neuropsychiatric Clinic, Skåne University Hospital, Malmö (Drs Buchhave, Minthon, Wallin, and Hansson); and Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal (Drs Zetterberg and Blennow), Sweden.
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
|
