Labeling of cerebral amyloid beta deposits in vivo using intranasal basic fibroblast growth factor and serum amyloid P component in mice.
There is currently no method for noninvasive imaging of amyloid beta (Abeta) deposition in Alzheimer's disease (AD). Because Abeta plaques are characteristic of AD and Abeta deposits contain abundant heparan sulfate proteoglycans that can bind basic fibroblast growth factor (bFGF) and serum amyloid P component (SAP), we investigated a novel route of ligand delivery to the brain to assess Abeta deposition in a transgenic (Tg) mouse model overexpressing Abeta-protein precursor.


METHODS
The biodistribution of bFGF injected intranasally was studied using (125)I-bFGF in Tg and wild-type control mice and by unlabeled bFGF and SAP immunocytochemistry with light and electron microscopy.


RESULTS
Three- to 5-fold higher amounts of (125)I-bFGF were found in the brain of Tg mice than that of wild-type mice (P < 0.05). bFGF or SAP given intranasally labeled cerebral Abeta plaques in the cortex and microvessels of Tg mice but not in wild-type mice. Weak bFGF staining and no SAP staining were detected in Tg mice without intranasal injection of the ligands. bFGF and SAP stained neurons around the rim of Abeta deposits and throughout the cortex in Tg mice. There was only weak staining of neurons in Tg mice without intranasal injection of bFGF and no staining of SAP in Tg mice without intranasal injection of SAP. No bFGF or SAP staining was evident in wild-type control mice.


CONCLUSIONS
We report a novel noninvasive method for labeling Abeta plaques. This method may be modified for human studies using intranasal injection of radiolabeled ligands and imaging with SPECT or PET.
Shi
Jiong
J
Department of Neurology, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106-4962, USA.
Perry
George
G
Berridge
Marc S
MS
Aliev
Gjumrakch
G
Siedlak
Sandy L
SL
Smith
Mark A
MA
LaManna
Joseph C
JC
Friedland
Robert P
RP
D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011877:Radionuclide Imaging; D000683:Serum Amyloid P-Component / Q000008:administration & dosage; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D000683:Serum Amyloid P-Component; D016222:Fibroblast Growth Factor 2