Toward a multifactorial model of Alzheimer disease

NEUROBIOLOGY OF AGING

卷:33

Article

Storandt, Martha^1,2  Head, Denise^2,3  Fagan, Anne M.¹  Holtzman, David M.¹  Morris, John C.^1,4 

[1] Washington Univ, Dept Neurol, St Louis, MO 63130 USA

[2] Washington Univ, Dept Psychol, St Louis, MO USA

[3] Washington Univ, Dept Radiol, St Louis, MO USA

[4] Washington Univ, Dept Pathol & Immunol Phys Therapy Occupat Therap, St Louis, MO USA

关键词: Preclinical Alzheimer disease;    Amyloid-beta;    Tau;    PIB;    Amyloid plaque;    APOE;    Brain volumetry;    Memory;    Biomarkers;    Cerebrospinal fluid;   

DOI  :  10.1016/j.neurobiolaging.2011.11.029

来源: Elsevier

【 摘 要 】

Relations among antecedent biomarkers of Alzheimer disease (AD) were evaluated using causal modeling; although correlation cannot be equated to causation, causation does require correlation. Individuals aged 43 to 89 years (N = 220) enrolled as cognitively normal controls in longitudinal studies had clinical and psychometric assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and brain amyloid imaging via positron emission tomography with Pittsburgh Compound B (PIB) obtained within 1 year. CSF levels of A beta(42) and tau were minimally correlated, indicating they represent independent processes. A beta(42), tau, and their interaction explained 60% of the variance in PIB. Effects of APOE genotype and age on PIB were indirect, operating through CSF markers. Only spurious relations via their common relation with age were found between the biomarkers and regional brain volumes or cognition. Hence, at least 2 independent hypothesized processes, one reflected by CSF A beta(42) and one by CSF tau, contribute to the development of fibrillar amyloid plaques preclinically. The lack of correlation between these 2 processes and brain volume in the regions most often affected in AD suggests the operation of a third process related to brain atrophy. (c) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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