RT Journal
A1 Buchhave P, Minthon L, Zetterberg H, Wallin ÅK, Blennow K, Hansson O
T1 CErebrospinal fluid levels ofβ-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of alzheimer dementia
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2012
FD January 1
VO 69
IS 1
SP 98
OP 06
DO 10.1001/archgenpsychiatry.2011.155
UL http://dx.doi.org/10.1001/archgenpsychiatry.2011.155
AB 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), andβ-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.