The Pathology of Alzheimer Disease Elicits an In Vivo Immunological Response
David J. Bonda, Kate M. Webber, Sandra L. Siedlak, George Perry, Robert P. Friedland and Mark A. Smith
DOI : 10.3844/ajisp.2007.10.14
American Journal of Immunology
Volume 3, Issue 1
The mechanism(s) responsible for the loss of neurons that characterizes Alzheimer disease is incompletely understood. Nonetheless, there is considerable evidence suggestive of immune abnormalities coupled to alterations in blood-brain barrier permeability that likely play a key role in both the etiology and progression of the disease. To examine these issues further, this study was designed to examine the presence of human antibodies within hippocampal regions of both diseased and normal brains. Specifically, using antibodies directed against either human lambda (λ) or kappa (κ) subunits of human IgG, we examined the amount and localization of endogenous human antibodies within the brain. In cases of Alzheimer disease, but not in age-matched controls, we found human antibodies associated with pyramidal neurons and dystrophic neurites surrounding amyloid plaques - pathological structures that characterize the disease. Since such human immunoglobulins likely originate in the vasculature, we also examined cases of cerebral amyloid angiopathy to further explore the importance of blood-brain barrier breaches and found high levels of antibodies associated with many blood vessels as well as pyramidal neurons. Taken together, these findings strengthen the notion that alterations in blood brain barrier permeability in both Alzheimer disease and cerebral amyloid angiopathy leads to the accumulation of antibodies that then may contribute to the inflammatory cascade within the brain.
© 2007 David J. Bonda, Kate M. Webber, Sandra L. Siedlak, George Perry, Robert P. Friedland and Mark A. Smith. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.