In vivo mapping of amyloid toxicity in Alzheimer disease.
OBJECTIVE
To study the relationship between gray matter atrophy and amyloid deposition in Alzheimer disease (AD).


METHODS
Volumetric magnetic resonance (MR) and [11C]-PIB PET were acquired from 23 patients with AD and 17 healthy older persons. Standardized [11C]-PIB uptake values were coregistered to MR scans in a standard space. Decreased density of and increased [11C]-PIB uptake in the gray matter of patients with AD vs controls were assessed with both voxel-based (p < 0.05 corrected) and region-of-interest (ROI) analyses. The relationship between decreased density of and increased [11C]-PIB uptake in the gray matter was investigated with voxel-based Pearson r maps (thresholded at p < 0.05) and ROI linear regression plots.


RESULTS
Atrophy mapped to the hippocampus and increased [11C]-PIB uptake to large frontal, parietal, and posterior cingulate cortical areas. ROI analysis showed the largest effect size for atrophy in the hippocampus (2.01) and amygdala (1.27) and the highest effect size for [11C]-PIB uptake in frontal (2.66), posterior cingulate/retrosplenial (2.43), insular (2.41), and temporal (2.23) regions. In the hippocampus, [11C]-PIB uptake was significantly increased, but effect size was milder (1.72). Significant correlations between atrophy and increased [11C]-PIB uptake were found in the hippocampal (r = -0.54) and amygdalar ROIs (r = -0.40) but not in the frontal, temporal, posterior cingulate/retrosplenial, insular, and caudate ROIs (r between 0.04 and 0.25).


CONCLUSIONS
The medial temporal lobe might be highly susceptible to amyloid toxicity, whereas neocortical areas might be more resilient.
Frisoni
G B
GB
Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio-FBF, via Pilastroni 4, I-25123 Brescia, Italy. gfrisoni@fatebenefratelli.it
Lorenzi
M
M
Caroli
A
A
Kemppainen
N
N
Någren
K
K
Rinne
J O
JO
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001284:Atrophy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles