Basic Science and Pathogenesis.

Background: Neurofibrillary tangles (NFTs), one of the hallmarks of Alzheimer's disease (AD), are composed of highly phosphorylated forms of the microtubule-associated protein tau. Phosphorylation results from the activity of several threonine/serine kinases, and increased expression of glycogen synthase kinase-3β (GSK-3β). These are involved in the formation of paired helical filament (PHF)-tau, which induces the formation of NFTs.

Retrospective analysis of Braak stage- and APOE4 allele-dependent associations between MR spectroscopy and markers of tau and neurodegeneration in cognitively unimpaired elderly.

Purpose: The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression.