Affiliations: [a] Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada
| [b] Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB, Canada
| [c] Department of Physics, University of Winnipeg, Winnipeg, MB, Canada
| [d] Department of Radiology, University of Manitoba, Winnipeg, MB, Canada
Correspondence:
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Correspondence to: Dr. Benedict C. Albensi and Wanda M. Snow, St. Boniface Hospital Research, Division of Neurodegenerative Disorders, 351 Tache Ave/R4050, Winnipeg, MB R2H 2A6, Canada. Tel.: +1 204 235 3941; Fax: +1 204 237 4092; E-mail: wsnow@sbrc.ca/wsnow 2001@yahoo.ca (W.M. Snow) and Tel.: +1 204 235 3942; Fax: +1 204 237 4092; E-mail: balbensi@sbrc.ca (B.C. Albensi).
Abstract: A diagnosis of Alzheimer’s disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo. Its utility in AD, however, is still under investigation. The current study used DTI to examine brain regions susceptible to AD-related pathology; the cerebral cortex, entorhinal cortex, and hippocampus, in 12-14-month-old 3xTg AD mice that possess both Aβ plaques and neurofibrillary tangles. Mean diffusivity did not differ between 3xTg and control mice in any region. Decreased fractional anisotropy (p < 0.01) and axial diffusivity (p < 0.05) were detected only in the hippocampus, in which both congophilic Aβ plaques and hyperphosphorylated tau accumulation, consistent with neurofibrillary tangle formation, were detected. Pathological tau accumulation was seen in the cortex. The entorhinal cortex was largely spared from AD-related neuropathology. This is the first study to demonstrate DTI abnormalities in gray matter in a mouse model of AD in which both pathological hallmarks are present, suggesting the feasibility of DTI as a non-invasive means of detecting brain pathology in vivo in early-stage AD.
