Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans.

Abstract:

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

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Fagan AM,Mintun MA,Mach RH,Lee SY,Dence CS,Shah AR,LaRossa GN,Spinner ML,Klunk WE,Mathis CA,DeKosky ST,Morris JC,Holtzman DM

doi

10.1002/ana.20730

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

512-9

issue

3

eissn

0364-5134

issn

1531-8249

journal_volume

59

pub_type

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