PAPER Lee S, Sato Y, Nixon RA

Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer's-like axonal dystrophy.

J Neurosci. 2011 May 25;31(21):7817-30. PubMed: 21613495

Barbara Tate on Smuggling Antibodies to BACE Across the Blood-Brain Barrier

COMMENT This pair of papers describes the efficacy of an antibody approach to inhibiting BACE1 activity, as well as an ingenious method for getting higher concentrations of therapeutic antibody into the brain. Passive immunization with a highly specific antibody

Dave Morgan on Smuggling Antibodies to BACE Across the Blood-Brain Barrier

COMMENT Here is my quick reaction to these intriguing papers, without the benefit of having had time to fully consider their impact. BACE1 is an intracellular target. This raises a level of challenge for antibody action beyond the blood-brain barrier, though it i

PAPER Luo X, Prior M, He W, Hu X, Tang X, Shen W, Yadav S, Kiryu-Seo S, Miller R, Trapp BD, Yan R

Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination.

J Biol Chem. 2011 Jul 8;286(27):23967-74. PubMed: 21576249

PAPER Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, Atwal J, Elliott JM, Prabhu S, Watts RJ, Dennis MS

Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target.

Sci Transl Med. 2011 May 25;3(84):84ra44. PubMed: 21613623

PAPER Atwal JK, Chen Y, Chiu C, Mortensen DL, Meilandt WJ, Liu Y, Heise CE, Hoyte K, Luk W, Lu Y, Peng K, Wu P, Rouge L, Zhang Y, Lazarus RA, Scearce-Levie K, Wang W, Wu Y, Tessier-Lavigne M, Watts RJ

A therapeutic antibody targeting BACE1 inhibits amyloid-β production in vivo.

Sci Transl Med. 2011 May 25;3(84):84ra43. PubMed: 21613622

Pieter Jelle Visser

Maastricht University; VU University Medical Centre
Maastricht, Netherlands

Stephen Salloway

Brown University
Providence, United States

Takeshi Iwatsubo on Smuggling Antibodies to BACE Across the Blood-Brain Barrier

COMMENT Reading the two excellent papers from Genentech, I was quite impressed by their elegant approach to raise anti-BACE1 antibodies that reduce Aβ production in vivo in brain. They further engineered the anti-BACE1 antibody by coupling it with a low-affinity

Ikram Ullah

Korea, Republic of

Hrishikesh Rangnekar

National AIDS Research Institute
Pune, India

Smuggling Antibodies to BACE Across the Blood-Brain Barrier

RESEARCH NEWS 2011-05-27 Research News The tight barrier between brain and blood vessels guards the brain from harm, but it also frustrates scientists trying to deliver therapeutic molecules to the central nervous system (CNS). In the May 25 Science Translational Medicine, resear

Lysosomal Block Clogs Transport, Swells Neurites

RESEARCH NEWS 2011-05-27 Research News In the brains of people with Alzheimer’s disease, misshapen neurons clog with organelles—ironically, the very ones in the autophagic-lysosomal system that normally help cells dispose of damaged organelles and protein waste. This abnormality

PAPER Ming GL, Song H

Adult neurogenesis in the mammalian brain: significant answers and significant questions.

Neuron. 2011 May 26;70(4):687-702. PubMed: 21609825

PAPER Grill JD, Ringman JM

Should persons with autosomal dominant AD be included in clinical trials?

Alzheimers Res Ther. 2011;3(3):18. PubMed: 21609419