Hi Mehmet,

As you have mentioned in the post, the BBB is one of the crucial limiting factor. Aβ is one of the factors that cause AD, and most of the antibody trials were targeting Aβ, but not specifically directed against oligomeric/toxic species of Aβ. Early detection and early therapeutic approach might be helpful.

1 ) It seems that  beta amyloide is rather a consequence of AD than the aetiologic main factor. So a clearance of ayloid deposits cdoes not affect  evolution of tne disease.  

Hi Mehmet,

my point of view about your inquisitive question to get opinions  about limited success of antibodies to AD , I propose you  to see my last presented work at Croatian Congress on Alzheimer's disease,2014. In Research Gate Lucijan Mohorovic, you can find my Poster Presentation : FERRIC IRON ACCUMULATION IN THE BRAIN - A NEW NANOTECHNOLOGY RESEARCH CHALLENGE.There you can find  my long time research interest and, the UCLA study at 2013, which confirm my statement  about the  role of Ferric iron . SATE OF THE ART  explain the recent opinion about  the new research needed about the Iron Brain accumulation  which is oposit to the standpoint of the current imunological research efforts.I hope that my opinion can at least partly satisfy your dilemma.

.Regards

Lucijan Mohorovic 

Robert Moulias, I think that is point should be clarified. The last data in the literature push us to ask the first question again; Aβ is cause or consequence of AD?

This is a question too vast to answer in a simple post. I would advise you to read some of the reviews on the subject. This one in Nature Reviews in Neurology is quite good:

http://www.ncbi.nlm.nih.gov/pubmed/24217510

This one is good too:

http://www.ncbi.nlm.nih.gov/pubmed/24252346

As AD leads to Aβ deposition so only targeting β is not the way to treat AD, For treating it we have to stop the cause behind this. So merely targeting Aβ by β antibody is not sufficient to treat the disease......

I apologize for my complicated discussion above. It is obvious that the immunological approach  have limited success of antibody to AD. A-beta brain harmful effects are undeniable conected with ferrous-ferric inversion which has an important part of Alzheimer disease's process.

Many a diseases display a lot of heterogeneity.  Same clinical picture can be caused by different factors which cannot be easily identified and hence pathogenesis can be different in different cases of the same disease.Certain infectious agents also induce widely different clinical presentations. Expression of different biological markers also varies in various diseases.Hence, any single therapeutic agent may not work for every case of a disease.

Your coment is significant but is insufficient to answer the question about  the limited success of anti-Abeta antibodies  to AD.It is well-known the conection with Abeta and ferrous-ferric inversion and the laboratory and clinical effects of this conection but with  existent unknowing   My point of view is that only red blood cell (RBC) are permanently present in human body from conception to the death and that  the  methemoglobin (MetHb) is the  valuable biomarker and source  of the ferric iron an  metabolic pathological degradation products  .This is the attitude of  mind and contribution to the research efforts to explain the sources and causes of the process of  pregnancy complication  AD, PD.Ms and other neurodegenerative diseases.

There may be several factors at work: (1) there was always a slightly better correlation for tangles, means tau, than beta-A4-amyloid; (2) by definition, the antibodies were given in AD, that means, there is already advanced neurodegeneration corresponding to Braak's stage III or IV. So they may have been given too late in the course of the disease.(3) intrathecal application may be fascinating, but carrying its own risk...

I think that fascination with amyloid in AD , and as a consequence with "anti amyloid" therapy, has something in common with the story of the  drunken man who is looking under the lamppost for his keys :" You lost them here ? - No, over there - But why do you look here ? - Because elsewhere I cannot see anything". 

Thank you for your nice example Jean :)