title: Clinical validity of A beta-protein deposition staging in brain aging and Alzheimer disease.
abstract: Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Abeta-protein staging based on the progression of amyloid deposition in the medial temporal lobe. To examine its clinical validity and evaluate whether it adds predictive power to NFT-based staging, we performed a study comparing both neuropathological classifications with clinical dementia rating scale (CDR) scores in a large autopsy series. The 2 neuropathological staging systems were strongly correlated. Their association with clinical severity was highly significant. However, the strength of the relationship was greater for NFT-based staging. It accounted for 26.5% of the variability in clinical severity, Abeta-protein-based staging for 13.0%, and age for 4.4%. Compared to NFT-based staging, the Abeta-protein-based system was less able to distinguish mild cognitive changes from dementia and showed marked overlap among the various stages of cognitive decline. In a multivariate model, NFT and age together accounted for 27.2% of the clinical variability and the addition of Abeta-protein deposition staging could only explain an extra 2.9%. Our data support the close relationship between NFT progression and amyloid formation within the medial temporal lobe proposed by Braak's group but demonstrate the limited value of Abeta-protein deposition staging in terms of clinicopathological correlations.
authors.affiliation: Department of Psychiatry, HUG Belle-Idée, University of Geneva School of Medicine, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Gold
authors.forename: E
authors.initials: E
authors.lastname: Kövari
authors.forename: G
authors.initials: G
authors.lastname: Corte
authors.forename: F R
authors.initials: FR
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Canuto
authors.forename: T
authors.initials: T
authors.lastname: Bussière
authors.forename: P R
authors.initials: PR
authors.lastname: Hof
authors.forename: C
authors.initials: C
authors.lastname: Bouras
authors.forename: P
authors.initials: P
authors.lastname: Giannakopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000544:Alzheimer Disease / Q000145:classification / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000145:classification / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides