Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Abstract

In vitro and in vivo 31P magnetic resonance (MR) spectroscopy studies of Alzheimer's disease (AD) brain have revealed alterations in membrane phospholipid metabolism and high-energy phosphate metabolism. Mildly demented AD patients compared with control subjects have increased levels of phosphomonoesters, decreased levels of phosphocreatine and probably adenosine diphosphate and an increased oxidative metabolic rate. As the dementia worsens, levels of phosphomonoesters decrease and levels of phosphocreatine and adenosine di-phosphate increase. The changes in oxidative metabolic rate suggest that the AD brain is under energetic stress. The phosphomonoester findings support our in vitro findings and implicate basic defects in membrane metabolism in AD brain. MR spectroscopy provides new diagnostic insights and a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.

Molecular Causes of the Aberrant Choline Phospholipid Metabolism in Breast Cancer

“…Collectively, these data indicate that diverse molecular alterations and treatments arrive at common end points in choline phospholipid metabolism of breast cancer. Aberrant choline phospholipid metabolism has also been demonstrated in inflammation-related pathologies (12,13) and neurological disorders, such as multiple sclerosis (14), Alzheimer's disease (15), and Gaucher's disease (16). Apoptosis has been linked to altered choline phospholipid metabolite concentrations as well (17).…”

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75NTR

“…137 Membrane biosynthesis could be compromised by specific allelic forms of ApoE, the main cholesterol carrier in the brain. 138 ApoE has been proposed to deliver lipids to neurites and growth cones for membrane biosynthesis in regenerating peripheral nerve, 139 and a virtual absence of NGF-dependent nerve sprouting has been observed in ApoE knock-out mice.…”

Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Dementias

“…14,16 Changes of PME (soluble membrane precursors) and PDE (membrane degradation products) reflect the biophysical states of membrane phospholipid, whereas Pi, PCr, and ATP are key metabolites involving energy metabolism. 16 Most in vivo and in vitro phosphorus MRS studies showed that PME and PDE were elevated in AD, 259,278-286 implying accelerated membrane turnover. Furthermore, in a comparative study using phosphorus MRS and histopathologic examination, Pettegrew et al 279 showed that PME intensity correlated inversely with the density of senile plaques in AD.…”

“…14 Changes in different metabolites reflect underlying brain pathology in dementia. [15][16][17] There are several published reviews of MRI 11-13 and MRS 15-18 relevant mainly to AD; the goal of this article is to review thoroughly recent advances of MRI and MRS in not only AD but also other neurodegenerative dementias and vascular dementia.…”