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


CONCLUSIONS
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.
Fagan
Anne M
AM
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. fagana@neuro.wustl.edu
Mintun
Mark A
MA
Mach
Robert H
RH
Lee
Sang-Yoon
SY
Dence
Carmen S
CS
Shah
Aarti R
AR
LaRossa
Gina N
GN
Spinner
Michael L
ML
Klunk
William E
WE
Mathis
Chester A
CA
DeKosky
Steven T
ST
Morris
John C
JC
Holtzman
David M
DM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D014018:Tissue Distribution
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)