Endpoints reached within 6 to 12 months of a study are essential. The amyloid-β hypothesis predicts that improved amyloid-β clearance should equate to slowing down the progression of the disease. In addition to neuroradiological tests of amyloid-β imaging (which maybe too expensive for large studies), CSF test (the ratio of amyloid-β1-42 and phospho-tau) is widely used in Europe and is economical. We have observed (Zhang et al., 2006) that immune testing of peripheral blood macrophages might be also helpful. The design of future studies should include both CSF and immune blood tests. The drugs likely work only in earlier stages of the disease.

References:
Zhang L, Fiala M, Cashman J, Sayre J, Espinosa A, Mahanian M, Zaghi J, Badmaev V, Graves MC, Bernard G, Rosenthal M. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2006 Sep;10(1):1-7. Abstract

View all comments by Milan Fiala

Amyloid-beta (Aβ) levels in the cerebrospinal fluid and interstitial fluid are controlled by complicated and partially known processes of production and clearance. Increases in Aβ levels result in nucleation and fibrillar formation of peptides, hence, plaque deposition. Zhang et al. (2006) showed that curcuminoids (a mixture of natural compounds) enhance uptake of Aβ; this may result in decreased Aβ levels, highlighting the usefulness of curcuminoids along with opening new areas for investigation.

In addition, a recent report by Cirrito et al. (2008) highlighted that the endocytosis of amyloid precursor protein into endosomes results in processing and release of Aβ into the interstitial space. Similarly, these authors also explained that, with increased synaptic activity, there is an increase in the endocytosis and in turn more Aβ release. Curcuminoids may command attention. They could be studied for their effect on the overall release of Aβ, as we are beginning to understand their role in clearance. These above-mentioned studies contributed significantly to existing...  Read more

Amyloid-beta (Aβ) levels in the cerebrospinal fluid and interstitial fluid are controlled by complicated and partially known processes of production and clearance. Increases in Aβ levels result in nucleation and fibrillar formation of peptides, hence, plaque deposition. Zhang et al. (2006) showed that curcuminoids (a mixture of natural compounds) enhance uptake of Aβ; this may result in decreased Aβ levels, highlighting the usefulness of curcuminoids along with opening new areas for investigation.

In addition, a recent report by Cirrito et al. (2008) highlighted that the endocytosis of amyloid precursor protein into endosomes results in processing and release of Aβ into the interstitial space. Similarly, these authors also explained that, with increased synaptic activity, there is an increase in the endocytosis and in turn more Aβ release. Curcuminoids may command attention. They could be studied for their effect on the overall release of Aβ, as we are beginning to understand their role in clearance. These above-mentioned studies contributed significantly to existing knowledge as well as unraveled potential pathways for drug targets in Alzheimer disease.

References:
Zhang L, Fiala M, Cashman J, Sayre J, Espinosa A, Mahanian M, Zaghi J, Badmaev V, Graves MC, Bernard G, Rosenthal M. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients. J Alzheimers Dis. 2006 Sep;10(1):1-7. Abstract

Cirrito JR, Kang JE, Lee J, Stewart FR, Verges DK, Silverio LM, Bu G, Mennerick S, Holtzman DM. Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron. 2008 Apr 10;58(1):42-51. Abstract

View all comments by Touqeer Ahmed