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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Authors | Rahul S Desikan, 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 |
Journal | Archives of neurology
(Arch Neurol)
Vol. 69
Issue 6
Pg. 709-13
(Jun 2012)
ISSN: 1538-3687 [Electronic] United States |
PMID | 22529247
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- Peptide Fragments
- amyloid beta-protein (1-42)
- tau Proteins
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Topics |
- Aged
- Aged, 80 and over
- Alzheimer Disease
(cerebrospinal fluid)
- Amyloid beta-Peptides
(cerebrospinal fluid)
- Canada
(epidemiology)
- Cohort Studies
- Disease Progression
- Female
- Humans
- Linear Models
- Male
- Peptide Fragments
(cerebrospinal fluid)
- Psychiatric Status Rating Scales
- United States
(epidemiology)
- tau Proteins
(cerebrospinal fluid)
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