Neurochemical and cognitive changes precede structural abnormalities in the TgF344-AD rat model.

Alzheimer's disease is a progressive neurodegenerative disorder with a decades-long pre-symptomatic phase, substantiating the need for prodromal biomarker development and early intervention. To deconstruct the processes underlying disease progression and identify potential biomarkers, we used neuroimaging techniques with high translational potential to human clinical studies in the TgF344-AD rat model which recapitulates the full spectrum of Alzheimer's neuropathology (progressive amyloid deposition, tauopathy, frank neuronal loss, gliosis, and cognitive dysfunction). We employed longitudinal MRI and magnetic resonance spectroscopy in conjunction with behavioural testing to characterize multiple facets of disease pathology in male and female TgF344-AD rats ( = 26, 14M/12F) relative to wildtype littermates ( = 24, 12M/12F).

Longitudinal characterization of neuroanatomical changes in the Fischer 344 rat brain during normal aging and between sexes.

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is one of the most frequently used models in aging research. Despite frequency of use, characterization of agerelated neuroanatomical change has not been performed in the F344 rat.

Longitudinal quantification of metabolites and macromolecules reveals age- and sex-related changes in the healthy Fischer 344 rat brain.

Normal aging is associated with numerous biological changes, including altered brain metabolism and tissue chemistry. In vivo characterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful noninvasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields; parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile.

An MRI-Derived Neuroanatomical Atlas of the Fischer 344 Rat Brain.

This paper reports the development of a high-resolution 3-D MRI atlas of the Fischer 344 adult rat brain. The atlas is a 60 μm isotropic image volume composed of 256 coronal slices with 71 manually delineated structures and substructures. The atlas was developed using Pydpiper image registration pipeline to create an average brain image of 41 four-month-old male and female Fischer 344 rats.

Distinct disruptions in Land's cycle remodeling of glycerophosphocholines in murine cortex mark symptomatic onset and progression in two Alzheimer's disease mouse models.

Changes in glycerophosphocholine metabolism are observed in Alzheimer's disease; however, it is not known whether these metabolic disruptions are linked to cognitive decline. Here, using unbiased lipidomic approaches and direct biochemical assessments, we profiled Land's cycle lipid remodeling in the hippocampus, frontal cortex, and temporal-parietal-entorhinal cortices of human amyloid beta precursor protein (ΑβPP) over-expressing mice. We identified a cortex-specific hypo-metabolic signature at symptomatic onset and a cortex-specific hyper-metabolic signature of Land's cycle glycerophosphocholine remodeling over the course of progressive behavioral decline.