***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Phosphorylation of tau protein at threonine 231 ( using full-length tau , 441 amino acids , for the numbering scheme ) ( p-tau(231 ) ) occurs specifically in postmortem brain tissue of patients with Alzheimer disease ( AD ) and can be sensitively detected in cerebrospinal fluid ( CSF ) . OBJECTIVES To determine to what extent CSF levels of p-tau(231 ) distinguish patients with AD from control subjects and from patients with other dementias , and to investigate whether p-tau(231 ) levels are a better diagnostic marker than levels of total tau protein ( t-tau ) in CSF . DESIGN AND SETTING Cross-sectional , multicenter , memory clinic-based studies . PARTICIPANTS One hundred ninety-two patients with a clinical diagnosis of AD , frontotemporal dementia ( FTD ) , vascular dementia , Lewy body dementia , or other neurological disorder and healthy controls . MAIN OUTCOME MEASURES Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays .  RESULTS Mean CSF levels of p-tau(231 ) were significantly elevated in the AD group compared with all other groups . Levels of p-tau(231 ) did not correlate with dementia severity in AD , and discriminated with a sensitivity of 90.2 % and a specificity of 80.0 % between AD and all non-AD disorders . Moreover , p-tau(231 ) levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls ( P = .03 ) and demented subjects ( P<.001 ) , particularly those with FTD ( P<.001 ) , but not those with vascular and Lewy body dementias . Sensitivity levels between AD and FTD were raised by p-tau(231 ) compared with t-tau levels from 57.7 % to 90.2 % at a specificity level of 92.3 % for both markers . CONCLUSION Increased levels of CSF p-tau(231 ) may be a useful , clinical ly applicable biological marker for the differential diagnosis of AD , particularly for distinguishing AD from FTD CONTEXT Small single-center studies have shown that cerebrospinal fluid ( CSF ) biomarkers may be useful to identify incipient Alzheimer disease ( AD ) in patients with mild cognitive impairment ( MCI ) , but large-scale multicenter studies have not been conducted . OBJECTIVE To determine the diagnostic accuracy of CSF beta-amyloid(1 - 42 ) ( Abeta42 ) , total tau protein ( T-tau ) , and tau phosphorylated at position threonine 181 ( P-tau ) for predicting incipient AD in patients with MCI . DESIGN , SETTING , AND PARTICIPANTS The study had 2 parts : a cross-sectional study involving patients with AD and controls to identify cut points , followed by a prospect i ve cohort study involving patients with MCI  , conducted 1990 - 2007 . A total of 750 individuals with MCI , 529 with AD , and 304 controls were recruited by 12 centers in Europe and the United States . Individuals with MCI  were followed up for at least 2 years or until symptoms had progressed to clinical dementia . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative likelihood ratios ( LRs ) of CSF Abeta42 , T-tau , and P-tau for identifying incipient AD . RESULTS During follow-up , 271 participants with MCI were diagnosed with AD and 59 with other dementias . The Abeta42 assay in particular had considerable intersite variability . Patients who developed AD had lower median Abeta42 ( 356 ; range , 96 - 1075 ng/L ) and higher P-tau ( 81 ; range , 15 - 183 ng/L ) and T-tau ( 582 ; range , 83 - 2174 ng/L ) levels than MCI patients who did not develop AD during follow-up ( 579 ; range , 121 - 1420 ng/L for Abeta42 ; 53 ; range , 15 - 163 ng/L for P-tau ; and 294 ; range , 31 - 2483 ng/L for T-tau , P < .001 ) . The area under the receiver operating characteristic curve was 0.78 ( 95 % confidence interval [ CI ] , 0.75 - 0.82 ) for Abeta42 , 0.76 ( 95 % CI , 0.72 - 0.80 ) for P-tau , and 0.79 ( 95 % CI , 0.76 - 0.83 ) for T-tau . Cut-offs with sensitivity set to 85 % were defined in the AD and control groups and tested in the MCI group , where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 % ( 95 % CI , 78%-88 % ) , specificity 72 % ( 95 % CI , 68%-76 % ) , positive LR , 3.0 ( 95 % CI , 2.5 - 3.4 ) , and negative LR , 0.24 ( 95 % CI , 0.21 - 0.28 ) . The positive predictive value was 62 % and the negative predictive value was 88 % . CONCLUSIONS This multicenter study found that CSF Abeta42 , T-tau , and P-tau identify incipient AD with good accuracy , but less accurately than reported from single-center studies . Intersite assay variability highlights a need for st and ardization of analytical techniques and clinical procedures We studied  CSF-tau and CSF-Abeta42  in 16 patients with mild cognitive impairment ( MCI ) who at follow-up investigations 6 - 27 months later had progressed to Alzheimer 's disease ( AD ) with dementia . For comparison , we studied 15 age-matched healthy individuals . At baseline , 14/16 ( 88 % ) of MCI patients had high CSF-tau and /or low CSF-Abeta42 levels . These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD . This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase Cerebrospinal fluid ( CSF ) biochemical diagnostic markers may be valuable to help in the diagnosis early in the course of Alzheimer 's disease ( AD ) , especially in the phase before clinical ly overt dementia , i.e. in patients with mild cognitive impairment ( MCI ) . We studied 44 patients with MCI who , at 1-year follow-up investigation , had progressed to AD with dementia , and 32 controls . Three CSF biomarkers related to the central pathogenic processes in AD were analysed , including CSF total-tau ( T-tau ) ( as a marker for neuronal degeneration ) , CSF phospho-tau ( P-tau ) ( as a marker for hyperphosphorylation of tau and possibly for the formation of neurofibrillary tangles ) , and CSF A beta 42 ( as a marker for A beta metabolism , and possibly for the formation of senile plaques ) . At baseline , 35/44 ( 79.5 % ) of the MCI patients had high CSF T-tau , 31/44 ( 70.4 % ) high CSF P-tau , while 34/44 ( 77.3 % ) had low CSF-A beta 42 levels . The positive likelihood ratio was 8.45 for CSF T-tau , 7.49 for CSF P-tau and 8.20 for CSF A beta 42 . These findings suggest that these CSF-markers are abnormal before the onset of clinical dementia , and that they may help to identify MCI patients that will progress to AD . CSF diagnostic markers will be especially important when drugs with potential effects on the progression of AD ( e.g. gamma-secretase inhibitors ) will reach the clinical phase In this report we evaluated the clinical performance of APOE genotyping and three protein biomarkers ( total tau , beta-amyloid(1 - 42 ) , and tau phosphorylated at threonine 181 ) in a prospect i ve multicenter study using the INNO-BIA AlzBio3 assay applied on Luminex platform . Concentration of biomarkers of Alzheimer 's disease in cerebrospinal fluid ( CSF ) was measured with multiplexing technology ( n=223 ) , and compared to the results of ELISA assays in patients with early dementias or mild cognitive impairment ( MCI ) collected at 12 gerontopsychiatric university departments , and APOE genotyping was performed .  Concentrations of Abeta(1 - 42 ) were statistically significantly lower in MCI-AD subjects compared to MCI-O , and significantly lower in D-AD patients compared to MCI-O. P-tau(181P ) concentrations were significantly higher in MCI-AD patients compared to MCI-O , and significantly higher in D-AD patients compared to MCI-O. The total tau concentrations in MCI-AD patients were significantly higher compared to MCI-O , and higher in D-AD compared to MCI-O , moreover , the concentration of total tau was significantly higher in D-AD compared to MCI-AD patients . For the differential diagnosis between D-AD and D-O , the optimal cutoff concentration of Abeta(1 - 42 ) was 197.7 pg/mL , and that for P-tau(181P ) was 47.9 pg/mL. These cutoff values were also applied to discriminate between MCI-AD and MCI-O subjects . Simultaneous measurement of the biomarkers significantly improves management of the sample s and quality control of the assays ' performance 
    Output:
    
Overall , the CSF Aβ1 - 42 levels were reduced in AD compared to controls or non-AD dementia .
Reduced CSF Aβ1 - 42 levels are of potential utility in the differential diagnosis of AD versus non-AD dementias and controls .
Diagnostic accuracy was high in AD versus healthy controls .
However , differential diagnosis for MCI or non-AD might be evaluated by other biomarkers