Regional cerebral glucose uptake in the 3xTG model of Alzheimer's disease highlights common regional vulnerability across AD mouse models.
We have previously used fluorodeoxyglucose (FDG) autoradiography to detect the pattern of metabolic declines in two different transgenic mouse models of fibrillar beta-amyloid pathology in Alzheimer's disease (AD), including the PDAPP mouse, which overexpresses a mutant form of human APP, and the PSAPP mouse, which overexpresses mutant forms of the human APP and PS1 genes. In this study, we used the same approach to study a triple-transgenic (3xTG) model of AD, which overexpresses human APP, PS1 and tau mutations, and progressively develops amyloid plaques, neurofibrillary tangles, and synaptic dysfunction. Densitometric measurements from 55 brain regions were characterized and compared in 2, 12, and 18 month-old 3xTG and wildtype control mice (n = 12/group). By 18 months of age, the 3xTG mice had significant reductions in FDG uptake in every measured brain region, including cortical and subcortical gray matter, cerebellar and brainstem regions. However, regional differences in normalized FDG uptake were apparent in the 2- and 12-month-old 3xTG mice, in a brain network pattern reminiscent of our previous analyses in the other mouse models. This prominently included the posterior cingulate/retrosplenial cortex, as in each previously-analyzed model. Overall, our analyses highlight consistencies in brain glucose uptake abnormalities across multiple mouse models of amyloid-associated pathophysiology. These mouse brain regional changes are homologous to alterations seen in PET scans from human AD patients and could thus be useful biomarkers for early testing of novel interventions.
Nicholson
Rachel M
RM
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center, Phoenix, Arizona, USA.
Kusne
Yael
Y
Nowak
Lee A
LA
LaFerla
Frank M
FM
Reiman
Eric M
EM
Valla
Jon
J
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D011877:Radionuclide Imaging; D016875:tau Proteins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose