High Cerebrospinal Fluid Tau and Low Amyloid β42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype
Doug R. Galasko,Linda Chang,Ruth Motter,Christopher M. Clark,J. A. Kaye,David S. Knopman,Ronald G. Thomas,Dora Kholodenko,Dale Schenk,I. Lieberburg,Bruce L. Miller,Robert C. Green,R. Basherad,L. Kertiles,M. A. Boss,P. Seubert +15 more
TLDR
Combined analysis of CSF Abeta42 and tau levels discriminated patients with AD, including patients with mild dementia, from the NC group, supporting use of these proteins to identify AD and to distinguish early AD from aging.Abstract:
Objective To evaluate cerebrospinal fluid (CSF) levels of amyloid β protein ending at amino acid 42 (Aβ42) and tau as markers for Alzheimer disease (AD) and to determine whether clinical variables influence these levels. Design Cohort study. Setting Six academic research centers with expertise in dementia. Subjects Eighty-two patients with probable AD, including 24 with very mild dementia (Mini-Mental State Examination score >23/30) (AD group); 60 cognitively normal elderly control subjects (NC group); and 74 subjects with neurological disorders, including dementia (ND group). Main Outcome Measures Levels of Aβ42 and tau were compared among AD, NC, and ND groups. Relationships of age, sex, Mini-Mental State Examination score, and apolipoprotein E (Apo E) genotype with these levels were examined using multiple linear regression. Classification tree models were developed to optimize distinguishing AD from NC groups. Results Levels of Αβ42 were significantly lower, and levels of tau were significantly higher, in the AD group than in the NC or ND group. In the AD group, Αβ42 level was inversely associated with Apo E ϵ 4 allele dose and weakly related to Mini-Mental State Examination score; tau level was associated with male sex and 1 Apo E ϵ 4 allele. Classification tree analysis, comparing the AD and NC subjects, was 90% sensitive and 80% specific. With specificity set at greater than 90%, the tree was 77% sensitive for AD. This tree classified 26 of 74 members of the ND group as having AD. They had diagnoses difficult to distinguish from AD clinically and a high Apo E ϵ 4 allele frequency. Markers in CSF were used to correctly classify 12 of 13 patients who later underwent autopsy, including 1 with AD not diagnosed clinically. Conclusions Levels of CSF Αβ42 decrease and levels of CSF tau increase in AD. Apolipoprotein E ϵ 4 had a dose-dependent relationship with CSF levels of Αβ42, but not tau. Other covariates influenced CSF markers minimally. Combined analysis of CSF Αβ42 and tau levels discriminated patients with AD, including patients with mild dementia, from the NC group, supporting use of these proteins to identify AD and to distinguish early AD from aging. In subjects in the ND group with an AD CSF profile, autopsy follow-up will be required to decide whether CSF results are false positive, or whether AD is a primary or concomitant cause of dementia.read more
Citations
More filters
Journal ArticleDOI
Mild cognitive impairment
Serge Gauthier,Barry Reisberg,Michael Zaudig,Ronald C. Petersen,Karen Ritchie,Karl Broich,Sylvie Belleville,Henry Brodaty,David A. Bennett,Howard Chertkow,Jeffrey L. Cummings,Mony J. de Leon,Howard Feldman,Mary Ganguli,Harald Hampel,Philip Scheltens,Mary C. Tierney,Peter J. Whitehouse,Bengt Winblad +18 more
TL;DR: Mild cognitive impairment can be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension.
Journal ArticleDOI
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
Leslie M. Shaw,Hugo Vanderstichele,Malgorzata Knapik-Czajka,Christopher M. Clark,Paul S. Aisen,Ronald C. Petersen,Kaj Blennow,Holly Soares,Adam J. Simon,Piotr Lewczuk,Robert A. Dean,Eric Siemers,William Z. Potter,Virginia M.-Y. Lee,John Q. Trojanowski +14 more
TL;DR: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.
Journal ArticleDOI
Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology
Rachelle S. Doody,James C. Stevens,Cornelia Beck,Richard Dubinsky,Jeffrey Kaye,Lisa P. Gwyther,Richard C. Mohs,Leon J. Thal,Peter J. Whitehouse,Steven T. DeKosky,Jeffrey L. Cummings +10 more
TL;DR: Dementia criteria for dementia have improved since the 1994 practice parameter, and further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.
Journal ArticleDOI
Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer’s Disease
Lih-Fen Lue,Yu Min Kuo,Alex E. Roher,Libuse Brachova,Yong Shen,Lucia I. Sue,Thomas G. Beach,Janice H. Kurth,Russel E. Rydel,Joseph Rogers +9 more
TL;DR: Investigation revealed that Aβ40, whether in soluble or insoluble form, was a particularly useful measure for classifying ND, HPC, and AD patients compared with Aβ42, and it was found that concentrations of soluble Aβ clearly distinguished HPC from AD patients and were a strong inverse correlate of synapse loss.
Journal ArticleDOI
Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.
Sid Gilman,Martin Koller,Ronald Black,L. Jenkins,S. G. Griffith,Nick C. Fox,L. Eisner,L. C. Kirby,M. Boada Rovira,Françoise Forette,Jean-Marc Orgogozo +10 more
TL;DR: This phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis provides an indication that Aβ immunotherapy may be useful in Alzheimer disease.
References
More filters
Journal ArticleDOI
“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
A practical method for grading the cognitive state of patients for the clinician
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Journal ArticleDOI
Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Journal ArticleDOI
Classification and Regression Trees.
Book
Classification and regression trees
TL;DR: The methodology used to construct tree structured rules is the focus of a monograph as mentioned in this paper, covering the use of trees as a data analysis method, and in a more mathematical framework, proving some of their fundamental properties.