Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional brain imaging studies of transgenic mouse models of Alzheimer's Disease.
Fluorodeoxyglucosepositron emission tomography (PET) studies find that persons with Alzheimer's disease have preferential reductions in posterior cingulate activity. Using fluorodeoxyglucose autoradiography, we found that transgenic mice overexpressing a mutant form of the human amyloid precursor protein have preferentially reduced activity in the same region, providing a potential brain imaging indicator of Alzheimer's disease in these animals. In this study, we considered the feasibility of using in vivo imaging techniques, such as PET, to detect this reduction despite their limitations in spatial resolution. Autoradiographic measurements of posterior cingulate activity were remeasured in the previously studied PDAPP transgenic and littermate control mice after the images were filtered to lower spatial resolutions. We continued to detect significantly lower cingulate activity in the transgenic mice when the images were blurred to 0.50 mm, failed to detect significantly abnormal activity when the images were blurred to 0.75 mm, and, indeed, found significantly higher activity when the images were blurred to 1.0 mm. Reversal in direction of the abnormality appears attributable to a previously observed truncation in the corpus callosum in PDAPP mice. With the possible exception of future in vivo imaging techniques that have a spatial resolution greater than or equal to 0.50 mm and high sensitivity, noninvasive functional brain imaging techniques like PET may not be suitable for detecting declines in regional activity in PDAPP mice. It remains possible that these imaging techniques will prove useful in transgenic mouse lines that do not exhibit the same morphological abnormalities in neighboring white matter regions.
Valla
J
J
Alzheimer's Disease Research Laboratory, Harrington Arthritis Research Center, USA.
Chen
K
K
Berndt
J D
JD
Gonzalez-Lima
F
F
Cherry
S R
SR
Games
D
D
Reiman
E M
EM
D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D019788:Fluorodeoxyglucose F18; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008822:Mice, Transgenic; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed
D016564:Amyloid beta-Protein Precursor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18