Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans

Abstract

Objectives Amyloid‐β₄₂ (Aβ₄₂) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Aβ₄₂ is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Aβ₄₂ “sink,” hindering transport of soluble Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ level, and those with negative PIB binding had the highest CSF Aβ₄₂ level. No relation was observed between PIB binding and CSF Aβ₄₀, tau, phospho‐tau₁₈₁, plasma Aβ₄₀, or plasma Aβ₄₂. Importantly, PIB binding and CSF Aβ₄₂ did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB‐positive with low CSF Aβ₄₂, 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 Aβ₄₂, and that amyloid imaging and CSF Aβ₄₂ may potentially serve as antecedent biomarkers of (preclinical) AD. Ann Neurol 2006