CLEARANCE OF ABETA 5/10/06

- Once formed, Abeta is mainly broken down by neprilysin 

(Yasojima K, McGeer EG, McGeer PL (2001) Relationship between beta amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain. Brain Res, 919, 115-21)

 Mice knock out with neprelysin gene are not able to clear Abeta.

- IDE (insulin degrading enzyme) appears to degrade intracellular Abeta more effectively than does NEP  (Biochemistry. 41(4): 1091-9, 2002)

-Plasmin is also a good candidate.  see:

Furthermore, the PLAU gene (urokinase-plasminogen activator gene is associated with risk for LOAD and accounts for the linkage finding on chromosome 10 (Younkin et al, 2002).

Tucker HM, ... , Estus S. Urokinase-type plasminogen activator inhibits amyloid-beta neurotoxicity and fibrillogenesis via plasminogen., J Neurosci Res  2002 Oct;70(2):249-55

Abeta can be captured by macrophages

Yazawa H, Yu ZX, Takeda, Le Y, Gong W, Ferrans VJ, et al. (2001) Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. Faseb J, 15, 2454-62.

Microglial reaction is important to remove Abeta aggregates: see vaccination

French Quarter: Le vaccin anti-Alzheimer fait actuellement l'objet d'essais thérapeutiques. Son principe est basé sur le constat que la production d'anticorps anti-Ab provoque la disparition progressive des plaques amyloïdes. Les anticorps générés par la vaccination se fixent sur les dépôts amyloïdes, ce qui active ensuite les cellules microgliales qui vont alors digérer les agrégats amyloïdes. La réaction microgliale serait salutaire, pour éliminer les lésions indésirables, ce qui pourrait expliquer l'inefficacité des anti-inflammatoires.