AXONAL INJURY AND MEMBRANE-ALTERATIONS IN ALZHEIMERS-DISEASE SUGGESTED BY IN-VIVO PROTON MAGNETIC-RESONANCE SPECTROSCOPIC IMAGING

We used spin-echo magnetic resonance imaging and proton magnetic reson ance spectroscopic imaging in 8 patients with probable Alzheimer's dis ease and in 10 age-matched elderly control subjects to assess the effe cts of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to t he control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal market), of chol ine residues representing lipid metabolites, and of creatine-containin g metabolites in a large section of the centrum semiovale containing w hite and mesial gray matter. Throughout the white matter of the patien ts with Alzheimer's disease compared to elderly control subjects, N-ac etylaspartate was decreased relative to choline (N-acetylaspartate-cho line ratio) and creatine-containing metabolites (N-acetylaspatate-crea tine ratio) with no changes in the choline-creatine ratio. The N-acety laspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The po sterior section of the centrum semiovale in the patients showed increa sed choline-creatine and choline-N-acetylaspartate ratios with the N-a cetylaspartate-creatine ratio unchanged between the patients and contr ol subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matte r of the centrum semiovale in patients with Alzheimer's disease.