Amyloid-beta expression in retrosplenial cortex of triple transgenic mice: relationship to cholinergic axonal afferents from medial septum.
Triple transgenic (3xTg-AD) mice harboring the presenilin 1, amyloid precursor protein, and tau transgenes (Oddo et al., 2003b) display prominent levels of amyloid-beta (Abeta) immunoreactivity in forebrain regions. The Abeta immunoreactivity is first seen intracellularly in neurons and later as extracellular plaque deposits. The present study examined Abeta immunoreactivity that occurs in layer III of the granular division of retrosplenial cortex (RSg). This pattern of Abeta immunoreactivity in layer III of RSg develops relatively late, and is seen in animals older than 14 months. The appearance of the Abeta immunoreactivity is similar to an axonal terminal field and thus may offer a unique opportunity to study the relationship between afferent projections and the formation of Abeta deposits. Axonal tract tracing techniques demonstrated that the pattern of axon terminal labeling in layer III of RSg, following placement of DiI in medial septum, is remarkably similar to the pattern of cholinergic axons in RSg, as detected by acetylcholinesterase histochemical staining, choline acetyltransferase immunoreactivity, or p75 receptor immunoreactivity; this pattern also is strikingly similar to the band of Abeta immunoreactivity. In animals sustaining early damage to the medial septal nucleus (prior to the advent of Abeta immunoreactivity), the band of Abeta in layer III of RSg does not develop; the corresponding band of cholinergic markers also is eliminated. In older animals (after the appearance of the Abeta immunoreactivity) damage to cholinergic afferents by electrolytic lesions, immunotoxin lesions, or cutting the cingulate bundle, result in a rapid loss of the cholinergic markers and a slower reduction of Abeta immunoreactivity. These results suggest that the septal cholinergic axonal projections transport Abeta or amyloid precursor protein (APP) to layer III of RSg.
Robertson
R T
RT
Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA. rtrobert@uci.edu
Baratta
J
J
Yu
J
J
LaFerla
F M
FM
D000109:Acetylcholine / Q000378:metabolism; D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002232:Carbocyanines; D002799:Cholinergic Fibers / Q000378:metabolism*; D004195:Disease Models, Animal; D006179:Gyrus Cinguli / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D056347:Neuroanatomical Tract-Tracing Techniques; D053764:Presenilin-1 / Q000235:genetics; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics
C035005:3,3'-dihexadecylindocarbocyanine; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002232:Carbocyanines; D053764:Presenilin-1; D016875:tau Proteins; D000109:Acetylcholine