Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization.

Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization. Research Abstract Details 

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Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization. Abstract Text:

Wan-Pin Chang,Deborah Downs,Xiang-Ping Huang,Huining Da,Kar-Ming Fung,Jordan Tang,Wan-Pin Chang,Deborah Downs,Xiang-Ping Huang,Huining Da,Kar-Ming Fung,Jordan Tang,

Memapsin 2 (beta-secretase, BACE1) is the protease that initiates cleavage of beta-amyloid precursor protein leading to the production of amyloid-beta (Abeta) and the onset of Alzheimer's disease (AD). Reducing Abeta by targeting memapsin 2 is a major strategy in developing new AD therapy. Here, in a proof-of-concept study, we show that immunization of transgenic AD mice (Tg2576) with memapsin 2 resulted in Abeta reduction and cognitive improvement. To study the basis of this therapy, we demonstrated that anti-memapsin 2 (anti-M2) antibodies were rapidly internalized and reduced Abeta production in cultured cells. These antibodies also effectively crossed the blood-brain barrier to reach the brain. Two- and 10-month Tg2576 mice were immunized and monitored over 10 and 6 months, respectively. We observed a significant decrease of plasma and brain Abeta40 and Abeta42 (approximately 35%) in the immunized mice as compared to controls. Immunized mice also showed better cognitive performance than controls in both cohorts. Brain histological analyses found no evidence of T cell/microglia/astrocyte activation in the immunized mice, suggesting the absence of inflammatory responses. These results suggest that memapsin 2 immunization in Tg2576 was effective in reducing Abeta production and improving cognitive function and that the current approach warrants further investigation as a therapy for AD.

Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization. Publishing Authors By Initials

WP Chang,D Downs,XP Huang,H Da,KM Fung,J Tang,WP Chang,D Downs,XP Huang,H Da,KM Fung,J Tang,

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Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 3184-96

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 10

MONTH: 05

YEAR: 2007

Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization. Information

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LANGUAGE: eng

NlmUniqueID: 8804484

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Grant and Affiliation Information for Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization.

AFFILIATION: Protein Studies Program, Oklahoma Medical Research Foundation, 825 N.E. 13th St., Oklahoma City, OK 73104, USA. wanpin-chang@omrf.ouhsc.edu

Country: United States

AGENCY: United States NCRR

GRANT: P20 RR 15577-07

ACRONYM: RR

MEDLINETA: FASEB J

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