Journal of Alzheimer's Disease - Volume 10, issue 4 - Journals

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Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus)

Article Type: Research Article

Abstract: Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-β (Aβ) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+ -dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We …found that 30% CR resulted in reduced contents of Aβ1-40 and Aβ1-42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Aβ peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-β protein precursor (AβPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of α- but not β- or γ- secretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD. Show more

Keywords: Calorie restriction, Alzheimer's disease, amyloid, Squirrel monkeys

DOI: 10.3233/JAD-2006-10411

Citation: Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 417-422, 2006

Price: EUR 27.50

Dopamine-induced stress signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes is partially mediated via the i3 loop and antagonized by blueberry extract

Authors: Joseph, J.A. | Fisher, D.R. | Carey, A.N. | Neuman, A. | Bielinski, D.F.

Article Type: Research Article

Abstract: Muscarinic receptors (MAChRs) are intimately involved in various aspects of both neuronal and vascular functioning, and there is selective oxidative stress sensitivity (OSS) among MAChR subtypes, with M1, M2, and M4 showing > OSS. OSS was assessed by determining the loss of ability of the cell to extrude or sequester Ca2+ following oxotremorine-induced depolarization following exposure to dopamine (DA) subtypes in transfected COS-7 cells. This OSS can be prevented by pretreatment with blueberry (BB) extract. Present studies were carried out to determine BB treatment of the cells transfected with wild type, truncated or chimeric [where the i3 loop of …one receptor was switched with the i3 loop of the other; i.e., M1(M3i3) and M3(M1i3)] receptors would alter DA-induced changes in calcium buffering and would confer protection through alterations in pMAPK, pCREB or PKC signaling. These findings also suggest that BB may antagonize OS effects by lowering activation of pCREB and possibly PKCγ induced by DA. In the truncated and chimeric receptors, results indicated that BB reduced OSS in response to DA in M1-transfected cells. However, BBs were also effective in preventing these Ca2+ buffering deficits in cells transfected with M1 receptors in which the i3 loop had been removed, but only partially enhanced the protective effects of the M3 i3 loop in the M1(M3i3) chimerics. A similar partial effect of BBs was seen in the M3(M1i3) chimerics which showed increased OSS in response to DA. It appears that antioxidants found in BBs might be targeting additional sites on these chimerics to decrease OSS. Show more

DOI: 10.3233/JAD-2006-10412

Citation: Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 423-437, 2006

Price: EUR 27.50

Plasma amyloid-β, Aβ _1-42, load is reduced by haemodialysis

Authors: Rubio, Isabel | Caramelo, Carlos | Gil, Ascención | Dolores López, María | de Yébenes, Justo García

Article Type: Research Article

Abstract: Patients with chronic renal failure treated with haemodialysis have vascular risk factors that, in the general population, are associated with increased prevalence of Alzheimer's disease (AD). Patients in haemodialysis, however, present different kinds of dementia but they do not have an increased risk of AD. We have hypothesized that amyloid-β (Aβ)1-42 is washed out from plasma during the dialysis and that this procedure enhances Aβ elimination and reduces the risk of AD. We have measured plasma Aβ1-42 levels in 11 patients with renal failure, before and after haemodialysis. A single procedure reduced the plasma Aβ levels in all …subjects with a mean decrement of 30% of baseline. Since Aβ deposition could be altered by certain metals like Cu and Zn, we have also measured the effects of dialysis on the levels of these ions in plasma. We found no changes in levels of Cu and Zn after dialysis. Haemodialysis, therefore, reduces very effectively plasma Aβ without modifying Cu and Zn levels. The potential use of this strategy in patients with AD requires further investigation. Show more

Keywords: Amyloid, plasma, haemodialysis, dementia, therapy

DOI: 10.3233/JAD-2006-10413

Citation: Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 439-443, 2006

Price: EUR 27.50