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

Objectives. Amyloid-beta(42) (A beta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) A beta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an A beta(42) "sink," hindering transport of soluble A beta(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 A beta(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 A beta(42) level, and those with negative PIB binding had the highest CSF A beta(42) level. No relation was observed between PIB binding and CSF A beta(40), tau, phospho-tau(181), plasma A beta(40), or plasma A beta(42). Importantly, PIB binding and CSF A beta(42) did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB-positive with low CSF A beta(42), suggesting the presence of amyloid in the absence of cognitive impairment (ie, preclinical AD). Intopretation These observations suggest that brain amyloid deposition results in low CSF A beta(42), and that amyloid imaging and CSF A beta(42) may potentially serve as antecedent biomarkers of (preclinical) AD.