Amyloid-beta-Associated Clinical Decline Occurs Only in the Presence of Elevated P-tau

作者：Desikan Rahul S^*; McEvoy Linda K; Thompson Wesley K; Holland Dominic; Brewer James B; Aisen Paul S; Sperling Reisa A; Dale Anders M

来源：Archives of Neurology, 2012, 69(6): 709-713.

DOI：10.1001/archneurol.2011.3354

Objective: To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-beta (A beta) 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: Weexamined 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 A beta(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 CSFA beta(1-42) and longitudinal change in global CDR, CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSF p-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF A beta(1-42) on longitudinal clinical decline was not significantly different from 0.
Conclusions: In cognitively normal older individuals, A beta-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration. Arch Neurol. 2012; 69(6): 709-713. Published online April 23, 2012. doi:10.1001/archneurol.2011.3354

• 出版日期2012-6