Active and passive immunotherapy for neurodegenerative disorders.

Abstract:

:Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cell-mediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.

journal_name

Annu Rev Neurosci

authors

Brody DL,Holtzman DM

doi

10.1146/annurev.neuro.31.060407.125529

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

175-93

eissn

0147-006X

issn

1545-4126

journal_volume

31

pub_type

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