Norman R. Relkina, Paul Szaboab, Basia Adamiaka, Tuna Burguta, Carmen Monthea, Richard W. Lentc, Steven Younkind, Linda Younkind, Richard Schiffe, Marc E. Wekslerb


Received 5 August 2007; received in revised form 4 December 2007; accepted 21 December 2007. published online 22 February 2008.
Abstract

Intravenous immunoglobulin (IVIg) has been proposed as a potential agent for Alzheimer's disease (AD) immunotherapy because it contains antibodies against beta-amyloid (Aβ). We carried out an open label dose-ranging study in 8 mild AD patients in which IVIg was added to approved AD therapies for 6 months, discontinued, and then resumed for another 9 months. Infusions were generally well-tolerated. Anti-Aβ antibodies in the serum from AD patients increased in proportion to IVIg dose and had a shorter half-life than anti-hepatitis antibodies and total IgG. Plasma Aβ levels increased transiently after each infusion. Cerebrospinal fluid Aβ decreased significantly at 6 months, returned to baseline after washout and decreased again after IVIg was re-administered for an additional 9 months. Mini-mental state scores increased an average of 2.5 points after 6 months, returned to baseline during washout and remained stable during subsequent IVIg treatment. Our findings confirm and extend those obtained by Dodel et al. [Dodel, R.C., Du, Y., Depboylu, C., Hampel, H., Frolich, L., Haag, A., Hemmeter, U., Paulsen, S., Teipel, S.J., Brettschneider, S., Spottke, A., Nolker, C., Moller, H.J., Wei, X., Farlow, M., Sommer, N., Oertel, W.H., 2004. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 75, 1472–1474] from a 6-month trial of IVIg in 5 AD patients and justify further studies of IVIg for treatment of AD.
Keywords: Intravenous immunoglobulin, Alzheimer's disease, Amyloid beta peptides, Immunotherapy

NEUROBIOLOGY OF AGING: Volume 30, Issue 11, Pages 1728-1736 (November 2009)

Heiko Braaka, Kelly Del Tredicia, Udo Rüba, Rob A.I de Vosb, Ernst N.H Jansen Steurb, Eva Braaka†


Received 30 January 2002; received in revised form 23 April 2002; accepted 30 April 2002.
Abstract

Sporadic Parkinson’s disease involves multiple neuronal systems and results from changes developing in a few susceptible types of nerve cells. Essential for neuropathological diagnosis are α-synuclein-immunopositive Lewy neurites and Lewy bodies. The pathological process targets specific induction sites: lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays and cortical areas gradually become affected. The disease process in the brain stem pursues an ascending course with little interindividual variation. The pathology in the anterior olfactory nucleus makes fewer incursions into related areas than that developing in the brain stem. Cortical involvement ensues, beginning with the anteromedial temporal mesocortex. From there, the neocortex succumbs, commencing with high order sensory association and prefrontal areas. First order sensory association/premotor areas and primary sensory/motor fields then follow suit. This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
Keywords: Parkinson’s disease, Staging procedure, α-synuclein, Lewy bodies, Lewy neurites, Limbic system, Motor system

NEUROBIOLOGY OF AGING: Volume 30, Issue 11, Pages 1728-1736 (November 2009)