Vincent Marchesi on BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo.

COMMENT I agree with Martin and Gouras that this paper deserves serious study since it is an ambitious attempt to explore whether cleavage of APP at different subcellular sites determines whether Abeta peptides are ultimately toxic to the neurons in which the are

Jacob Mack on There’s Something FISHy About Aβ Toxicity

COMMENT I think we are getting off track abit. It has been established for some time that various phosphorylation processes occur in the presence of amyloid beta, including tau protein, tyrosine kinase receptors, involvement of g protins, etc... amongst others. T

Jacob Mack on Add Alzheimer's disease to the list of autoimmune diseases.

COMMENT as an efficient killer of neurons. I welcome comments and any related AD information through email to

George Martin on Wnt/beta-catenin pathway.

COMMENT This is a good opportunity for those of you who have not engaged with the Connections Maps of STKE Science of Aging Knowledge Environment to check out the WNT pathway. (Try the simplifed animated teaching version!) Randy Moon, a world expert on this incre

RICHARD NOWAK on Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease.

COMMENT I urge everyone to read this paper- it is a must read for anyone working in neurodegeneration. For the first time the possibility of early noninvasive detection of AD is on the visible horizon. 0 richard.nowak

Gunnar Gouras on BACE overexpression alters the subcellular processing of APP and inhibits Abeta deposition in vivo.

COMMENT EB Lee and colleagues provide very interesting data indicating that high BACE overexpression paradoxically reduces Aβ levels and plaque pathology in Tg2576 transgenic mice harboring the APP Swedish mutation. They employ diverse methods to demonstrate that

Bruce Yankner on There’s Something FISHy About Aβ Toxicity

COMMENT This paper provides insight into a potentially novel mechanism of Aβ toxicity. The authors start by looking for proteins in which phosphorylation is induced by toxic levels of Aβ in human cortical cultures. They identify the FISH (for Five SH3 domains) pr

George Martin on Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease.

COMMENT This paper reports the fruits of a wonderful collaboration between an Alzheimer researcher (Bill Klein) and a "nanochemist", Chad Mirkin, both at Northwestern University. It follows very important work by Bill Klein and his colleagues implicatin

Charles Glabe on Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta.

COMMENT Are conformation-dependent antibodies the key to a safe and effective AD immunotherapy? Although immunotherapy for AD has become very attractive and its effectiveness is being applauded, there are lingering safety concerns as scientists continue to work t

Massimo Tabaton on Salubrinal to the Rescue? New Compound Fights ER Stress

COMMENT This is a very interesting paper. Boyce and colleagues showed that pharmacological inhibition of dephosphorylation of eukaryotic initiator factor 2α increases its activity, thus protecting against the effects of ER stress. They also demonstrated that this

Einar Sigurdsson on Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta.

COMMENT The study by Racke and colleagues is the third report showing cerebral bleeding in different AD mouse models following passive immunization with monoclonal antibodies with high affinity for Aβ plaques and congophilic angiopathy (Pfeifer et al., 2002; Wilc

Mark Cookson on PD Models: Loss of DJ Throws D2 Dopamine Receptor Out of Step

COMMENT Recessive mutations, like those in DJ-1 that are associated with Parkinsonism, are great candidates for making knockout alleles in mice to try and model the disease, as well as understand normal gene function. In this paper, Matt Goldberg, Jie Shen, and t

Vijendra Singh on Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease.

COMMENT This is a very good paper for increased T cell reactivity in Alzheimer disease, but the authors failed to refer to previous research, including our own report of abnormal lymphocyte proliferation by amyloid protein-β in AD patients (Singh, 1994). I wish p

Dave Morgan on Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta.

COMMENT This article points out an important consideration with respect to passive immunotherapy against Aβ and its possible application to Alzheimer patients, namely, the increased risk for vascular hemorrhage with N-terminal-specific antibodies. Equally importa

Takaomi Saido on Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.

COMMENT Brendza and colleagues demonstrate that administration of anti-Aβ antibodies into APP-transgenic mouse brain results in recovery of dystrophic neuritis surrounding Aβ plaques. The authors employed multiphoton microscopy to detect dystrophic neuritis label