Title:Characterization of Myelin Pathology in the Hippocampal Complex of a Transgenic Mouse Model of Alzheimer’s Disease
VOLUME: 10 ISSUE: 1
Author(s):Larry C. Schmued, James Raymick, Merle G. Paule, Melanie Dumas and Sumit Sarkar
Affiliation:Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson AR 72079, USA.
Keywords:Alzheimer’s disease, amyloid plaques, Black-Gold II, demyelination, hippocampus, AD-Tg mouse
Abstract:We have characterized the myelin changes observed within the hippocampal complex (HC) of a transgenic (Tg)
mouse model of Alzheimer’s disease (AD). Individual myelinated fibers were labeled with Black-Gold II while amyloid
plaques were labeled with either Congo Red or Pan-A-beta immunofluoresence. Myelinated fibers were never seen passing
through amyloid plaques in any region, while conspicuous myelin pathology was seen within, and immediately adjacent
to, the amyloid plaques in the HC of the AD-Tg mouse. This pathology consisted of a complete disruption of myelinated
fibers passing through the plaque and the region immediately adjacent to the plaques exhibited an edematous swelling
of the fibers. This pathology was most frequently observed within the molecular and polymorph layers of the dentate
gyrus and the molecular layer of Ammon’s horn. The remaining layers of Ammon’s horn exhibited minimal myelin pathology,
while moderate myelinopathy was observed in the subiculum. Since the HC is integral for memory function,
these findings may help account for the memory problems so characteristic of the disease process. Because the molecular
layers of the dentate gyrus and Ammon’s horn are the sites of inputs to the HC, the extensive myelin pathology observed
in these regions would imply functional deafferentation of the HC. The appearance of some Black-Gold II positive debris
within the plaques may reflect a possible cascade mechanism whereby the presence of plaques results in myelin degeneration,
some of which is incorporated within the plaque, causing it to further expand in a self-perpetuating fashion.
