[(11)C]PIB-amyloid binding and levels of Abeta40 and Abeta42 in postmortem brain tissue from Alzheimer patients.
beta-Amyloid (Abeta) deposits are one of the major histopathological hallmarks of Alzheimer's disease (AD). The amyloid-imaging positron emission tomography (PET) tracer [(11)C]PIB (N-methyl[(11)C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole) is used in the assessment of Abeta deposits in the human brain. [(11)C]PIB-amyloid interaction and insoluble Abeta40 and Abeta42 peptide levels in the brain were quantified in postmortem tissue from nine AD patients and nine age-matched control subjects in the temporal, frontal and parietal cortices and the cerebellum. Autoradiographical studies showed significantly higher densities of specific [(11)C]PIB-amyloid binding in gray matter in the temporal and parietal cortex (62fmol/mg tissue) in AD patients as compared to control subjects, whereas the density was somewhat lower in the frontal cortex (56fmol/mg tissue). No specific binding could be detected in the AD cerebellum or in the tissues from the control subjects (< or =5fmol/mg tissue). Insoluble Abeta40 and total Abeta levels (i.e. sum of Abeta40 and Abeta42) were significantly higher in patients than in controls in all measured cortical regions as determined using ELISA, which was confirmed using immunohistochemistry. The present findings show a more regional selective distribution of [(11)C]PIB amyloid binding than previously reported. Moreover, it is suggested that some of the [(11)C]PIB binding and insoluble Abeta seen in control subjects may be amyloid in the blood vessels.
Svedberg
Marie M
MM
Uppsala University, Department of Biochemistry and Organic Chemistry, Sweden. marie.svedberg@biorg.uu.se
Hall
Håkan
H
Hellström-Lindahl
Ewa
E
Estrada
Sergio
S
Guan
ZhiZhong
Z
Nordberg
Agneta
A
Långström
Bengt
B
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000814:Aniline Compounds; D001345:Autoradiography; D052160:Benzothiazoles; D001667:Binding, Competitive / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)