Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ ₄₂ in humans

Abstract

Abstract Objectives Amyloid‐β 42 (Aβ 42 ) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Aβ 42 is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Aβ 42 “sink,” hindering transport of soluble Aβ 42 between brain and CSF. We investigated this hypothesis. Methods We compared the in vivo brain amyloid load (via positron emission tomography imaging of the amyloid‐binding agent, Pittsburgh Compound‐B [PIB]) with CSF Aβ 42 and other measures (via enzyme‐linked immunosorbent assay) in clinically characterized research subjects. Results Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF Aβ 42 level, and those with negative PIB binding had the highest CSF Aβ 42 level. No relation was observed between PIB binding and CSF Aβ 40 , tau, phospho‐tau 181 , plasma Aβ 40 , or plasma Aβ 42 . Importantly, PIB binding and CSF Aβ 42 did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB‐positive with low CSF Aβ 42 , suggesting the presence of amyloid in the absence of cognitive impairment (ie, preclinical AD). Interpretation These observations suggest that brain amyloid deposition results in low CSF Aβ 42 , and that amyloid imaging and CSF Aβ 42 may potentially serve as antecedent biomarkers of (preclinical) AD. Ann Neurol 2006

Keywords

Affiliated Institutions

• University of Pittsburgh US
• Hope Center for Neurological Disorders US
• Washington University in St. Louis US

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