Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Buchhave, P, Minthon, L, Zetterberg, H, Wallin, AK, Blennow, K, Hansson, O |
Journal | Arch Gen Psychiatry |
Volume | 69 |
Issue | 1 |
Pagination | 98-106 |
Date Published | 2012 Jan |
ISSN | 1538-3636 |
Keywords | Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Female, Follow-Up Studies, Humans, Male, Mild Cognitive Impairment, Peptide Fragments, Predictive Value of Tests, tau Proteins, Time Factors |
Abstract | 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 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. |
DOI | 10.1001/archgenpsychiatry.2011.155 |
Alternate Journal | Arch. Gen. Psychiatry |
PubMed ID | 22213792 |