Kumar Sambamurti on Peter Davies, Beloved Giant of Alzheimer’s Disease Research, Dies at 72

COMMENT With Peter's death, we have all lost a major leader in the AD field. It is really very sad. sambak 0 ...

Kumar Sambamurti on End of the BACE Inhibitors? Elenbecestat Trials Halted Amid Safety Concerns

COMMENT In agreement with several of the statements above, the clinical trial failure of BACE does not take away the importance of Aβ and senile plaques as key initiators of AD-associated dementia. I will emphasize that these disappointments are due to toxicity ...

Kumar Sambamurti on Merck Pulls Plug on Phase 2/3 BACE Inhibitor Trial

COMMENT Let us hope that prodromal AD will benefit from verubecestat treatment. A problem with even this relatively early stage of disease is that Aβ may have already accumulated, which will make a negative study difficult to interpret. This confound is in ...

Kumar Sambamurti on Field Loses Chad Dickey, 40, to Cancer

COMMENT It is really sad and sudden to lose a valuable and always cooperative colleague. sambak 0 ...

Kumar Sambamurti on Mutant Presenilin Knock-in Mice Mimic Knockouts, Stir Old Debate

COMMENT I would like to point out that loss and gain of function are really definitions dependent on the phenotype being assessed. We have always held that presenilin mutations represented an impairment of γ-secretase activity, and recognized a parallel between ...

Kumar Sambamurti on Scant α-Secretase Compensation for BACE Inhibition in Monkeys

COMMENT Inhibition of α-secretase does not affect BACE1 processing in neuroblastoma cells expressing endogenous APP (Gandhi et al., 2004). Thus, the two pathways don't appear to compensate for each other, but appear to occur in independent compartments. ...

Kumar Sambamurti on Proteomics Point to RNA Splicing Defects in Alzheimer’s

COMMENT This is a truly exciting advance. While the small RNA world has captured the attention of the field, the global spicing failure is very novel and has been ignored since the days of KPI containing APP forms. It is curious that the authors saw a large ...

Kumar Sambamurti on Larry Sparks, of Alzheimer’s-Cholesterol Fame, Dies at 63

COMMENT The controversy and research opportunities that Larry started on the role of cholesterol in AD pathogenesis lives on. He was also a really nice and friendly person. It is very sad to see him go. sambak 0 ...

Kumar Sambamurti on A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease.

COMMENT The binding of amyloid by RAGE has been an interesting development that has long been waiting to be exploited. Unfortunately, initial efforts have not been successful in clinical trials. This multimodal drug has particularly exciting possibilities, as it ...

Kumar Sambamurti on Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains.

COMMENT This represents a careful and significant study with clean results. It probably explains why γsecretase loses activity in Triton-X100 and helps in a more thorough functional characterization of the enzyme. sambak 0 ...

Kumar Sambamurti on A fragment of the scaffolding protein RanBP9 is increased in Alzheimer's disease brains and strongly potentiates amyloid-beta peptide generation.

COMMENT This is an exciting finding. sambak 0 ...

Kumar Sambamurti on Anne Cataldo, 57, Autophagy Researcher Known for Generous Collegiality

COMMENT It is impossible to give words to feelings under these conditions. Although my personal interactions with Ann were brief and periodic, they were extraordinarily memorable. She was kind, open and great for discussion. She will certainly be missed. Peter, I ...

Kumar Sambamurti on ApoE’s Secret Revealed? Protein Promotes Aβ Degradation

COMMENT Great findings. sambak 0 ...

Kumar Sambamurti on Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade.

COMMENT This is a truly exciting study that takes advantage of an Aβ-degrading enzyme to increase Aβ turnover. It is particularly useful as this enzyme can clip the oligomers. It will be very useful to know whether the treatment reduces pro-NGF and increases NGF ...

Kumar Sambamurti on Keystone Drug News: CoMentis BACE Inhibitor Debuts

COMMENT This will be exciting to watch and follow up. sambak 0 ...