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. 2012 Jun;69(6):709-13.
doi: 10.1001/archneurol.2011.3354.

Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau

Rahul S Desikan  1 , Linda K McEvoy, Wesley K Thompson, Dominic Holland, James B Brewer, Paul S Aisen, Reisa A Sperling, Anders M Dale; Alzheimer’s Disease Neuroimaging Initiative
Collaborators, Affiliations

Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau

Rahul S Desikan et al. Arch Neurol. 2012 Jun.

Abstract

Objective: To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals.

Design: A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.

Setting: Research centers across the United States and Canada.

Patients: We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.

Main outcome measures: Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale.

Results: We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0.

Conclusions: In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.

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Figures

Figure 1
Figure 1
Box and whisker plots for all participants illustrating change in (a) CDR-SB and (b) ADAS-cog scores, measured as annualized percent change (APC), based on CSF Aβ1-42 (Aβ) and CSF p-tau181p (pτ) status. For each plot, thick black lines show the median value. Regions above and below the black line show the upper and lower quartiles, respectively. The dashed lines extend to the minimum and maximum values with outliers shown as open circles. As illustrated, the Aβ +/pτ + individuals demonstrated the largest change in CDR-SB and ADAS-cog scores.
See this image and copyright information in PMC

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