Abstract:
:Amyloid-beta (Abeta) accumulation in senile plaques is a hallmark of Alzheimer's disease (AD). Immunotherapy is a leading approach for amyloid clearance, despite the early termination of the Elan clinical trial with active immunization due to a few cases of meningoencephalitis. The mechanisms of immunotherapy-mediated amyloid clearance and this deleterious side effect are largely unknown. While clearance of Abeta probably results in part from microglia-mediated inflammation, it can be microglia independent. Therefore, establishing the role of microglia in Abeta clearance is important for the treatment of AD. We analyzed the effects of direct microglia activation and inhibition on antibody-mediated Abeta clearance. Robust microglia activation with interferon-gamma led to modest Abeta clearance alone but did not potentiate antibody-mediated clearance. Microglia elimination/inactivation with immunotoxin or minocycline only partially limited antibody-induced Abeta clearance suggesting that although there is a role for microglia in Abeta clearance, it does not account for the majority of the effect observed after anti-Abeta antibody treatment.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Garcia-Alloza M,Ferrara BJ,Dodwell SA,Hickey GA,Hyman BT,Bacskai BJdoi
10.1016/j.nbd.2007.07.019subject
Has Abstractpub_date
2007-12-01 00:00:00pages
286-92issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(07)00167-2journal_volume
28pub_type
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