Brain Biomarkers in Familial Alzheimer’s Disease Mouse Models

Abstract

Alzheimer’s disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer’s disease (FAD). These deficits are readily detected in young adults, at 2–3 months of age, preceding amyloid deposition and cognitive impairments, which may indicate that impaired neurogenesis can be an early biomarker for cognitive deficits in AD. Recent studies suggest that NSC can be detected in live rodents, noninvasively, using proton magnetic resonance spectroscopy (1H-MRS) signal at 1.28 ppm. Here we examined the use of 1H-MRS for determining the extent of neurogenesis in the brains of FAD mice. We observed that the reduction in neurogenesis in the FAD mice as observed by immunohistochemistry, was not manifested by a reduction in the 1.28 ppm signal, suggesting that this marker is either not specific for neurogenesis or not sensitive enough for the detection of alterations in hippocampal neurogenesis in the brains of FAD mice.

Metabolite Profile of Alzheimer’s Disease in the Frontal Cortex as Analyzed by HRMAS 1H NMR

“…Nuclear magnetic resonance spectroscopy (NMR or MRS) allows for the in vivo and ex vivo measurement of metabolites in the brain and can thus potentially enable the non-invasive quantification of neurochemical alterations to gain information on progressive neuro-degeneration in AD brains (Kuttner-Hirshler et al, 2017; Mullins et al, 2018; Yeh et al, 2018). In earlier studies, in vivo MRS was used to evaluate the level of a number of neurochemicals, such as N -acetyl aspartate (NAA), mI, Cr, and phosphocreatine (PC), Cho, and Cho derivatives, and Gln/Glu (Glx) in the AD patient tissues.…”