Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG.
Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar Aβ. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar Aβ deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients.


METHODS
(11)C-DED PET was performed in MCI patients (n = 8; mean age ± SD, 62.6 ± 7.5 y; mean Mini Mental State Examination, 27.5 ± 2.1), AD patients (n = 7; mean age, 65.1 ± 6.3 y; mean Mini Mental State Examination, 24.4 ± 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 ± 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference.


RESULTS
ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers.


CONCLUSIONS
Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Stephen F
SF
Carter
Michael
M
Schöll
Ove
O
Almkvist
Anders
A
Wall
Henry
H
Engler
Bengt
B
Långström
Agneta
A
Nordberg
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003903:Deuterium; D005260:Female; D019788:Fluorodeoxyglucose F18; D005911:Gliosis / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D012189:Retrospective Studies; D012642:Selegiline; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D011849:Radioactive Tracers; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D012642:Selegiline; D003903:Deuterium; D008995:Monoamine Oxidase