Diet as a risk factor for Alzheimer's disease / Dieta jako czynnik ryzyka choroby Alzheimera.

Chronic exposure to an unhealthy diet is one of the causes of civilization diseases and significantly affects the average longevity. The impact of diet on health is extremely complicated due to the chemical diversity of its composition. The diet provides over 26,000 biochemicals and even more of their metabolites. Among this diversity, three macronutrients: proteins, carbohydrates and fats can be identified that provide energy, and in addition providing their metabolites. According to the latest concepts of the impact of macronutrients in diet on human health, their mutual proportions and not solely absolute quantities are of great importance. In our article we present a short discussion of our own research on this problem in relation to the incidence of Alzheimer's disease against the background of contemporary biochemical and epidemiological literature.

Correction: The Calculator of Anti-Alzheimer's Diet. Macronutrients.

[This corrects the article DOI: 10.1371/journal.pone.0168385.].

The Calculator of Anti-Alzheimer's Diet. Macronutrients.

The opinions about optimal proportions of macronutrients in a healthy diet have changed significantly over the last century. At the same time nutritional sciences failed to provide strong evidence backing up any of the variety of views on macronutrient proportions. Herein we present an idea how these proportions can be calculated to find an optimal balance of macronutrients with respect to prevention of Alzheimer's Disease (AD) and dementia. These calculations are based on our published observation that per capita personal income (PCPI) in the USA correlates with age-adjusted death rates for AD (AADR). We have previously reported that PCPI through the period 1925-2005 correlated with AADR in 2005 in a remarkable, statistically significant oscillatory manner, as shown by changes in the correlation coefficient R (Roriginal). A question thus arises what caused the oscillatory behavior of Roriginal? What historical events in the life of 2005 AD victims had shaped their future with AD? Looking for the answers we found that, considering changes in the per capita availability of macronutrients in the USA in the period 1929-2005, we can mathematically explain the variability of Roriginal for each quarter of a human life. On the basis of multiple regression of Roriginal with regard to the availability of three macronutrients: carbohydrates, total fat, and protein, with or without alcohol, we propose seven equations (referred to as "the calculator" throughout the text) which allow calculating optimal changes in the proportions of macronutrients to reduce the risk of AD for each age group: youth, early middle age, late middle age and late age. The results obtained with the use of "the calculator" are grouped in a table (Table 4) of macronutrient proportions optimal for reducing the risk of AD in each age group through minimizing Rpredicted-i.e., minimizing the strength of correlation between PCPI and future AADR.

Correlation of Alzheimer's disease death rates with historical per capita personal income in the USA.

Alzheimer's disease (AD) is a progressive degenerating disease of complex etiology. A variety of risk factors contribute to the chance of developing AD. Lifestyle factors, such as physical, mental and social activity, education, and diet all affect the susceptibility to developing AD. These factors are in turn related to the level of personal income. Lower income usually coincides with lower level of education, lesser mental, leisure-social and physical activity, and poorer diet. In the present paper, we have analyzed the correlation of historical (1929-2011) per capita personal income (PCPI) for all states of the USA with corresponding age-adjusted AD death rates (AADR) for years 2000, 2005 and 2008. We found negative correlations in all cases, the highest one (R ≈ -0.65) for the PCPIs in the year 1970 correlated against the AADRs in 2005. From 1929 to 2005 the R value varies in an oscillatory manner, with the strongest correlations in 1929, 1970, 1990 and the weakest in 1950, 1980, 1998. Further analysis indicated that this oscillatory behavior of R is not artificially related to the economic factors but rather to delayed biological consequences associated with personal income. We conclude that the influence of the income level on the AD mortality in 2005 was the highest in the early years of life of the AD victims. Overall, the income had a significant, lifelong, albeit constantly decreasing, influence on the risk of developing AD. We postulate that the susceptibility of a population to late-onset AD (LOAD) is determined to a large extent by the history of income-related modifiable lifestyle risk factors. Among these risk factors, inappropriate diet has a significant contribution.

Epileptogenesis following Kainic Acid-Induced Status Epilepticus in Cyclin D2 Knock-Out Mice with Diminished Adult Neurogenesis.

The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). Cyclin D2 knockout (cD2 KO) mice, which lack adult neurogenesis almost entirely, were used as a model. First, we examined whether status epilepticus (SE) evoked by an intra-amygdala injection of KA induces cell proliferation in cD2 KO mice. On the day after SE, we injected BrdU into mice for 5 days and evaluated the number of DCX- and DCX/BrdU-immunopositive cells 3 days later. In cD2 KO control animals, only a small number of DCX+ cells was observed. The number of DCX+ and DCX/BrdU+ cells/mm of subgranular layer in cD2 KO mice increased significantly following SE (p<0.05). However, the number of newly born cells was very low and was significantly lower than in KA-treated wild type (wt) mice. To evaluate the impact of diminished neurogenesis on epileptogenesis and early epilepsy, we performed video-EEG monitoring of wt and cD2 KO mice for 16 days following SE. The number of animals with seizures did not differ between wt (11 out of 15) and cD2 KO (9 out of 12) mice. The median latency to the first spontaneous seizure was 4 days (range 2-10 days) in wt mice and 8 days (range 2-16 days) in cD2 KO mice and did not differ significantly between groups. Similarly, no differences were observed in median seizure frequency (wt: 1.23, range 0.1-3.4; cD2 KO: 0.57, range 0.1-2.0 seizures/day) or median seizure duration (wt: 51 s, range 23-103; cD2 KO: 51 s, range 23-103). Our results indicate that SE-induced epileptogenesis is not disrupted in mice with markedly reduced adult neurogenesis. However, we cannot exclude the contribution of reduced neurogenesis to the chronic epileptic state.

Maintenance of long-term potentiation in hippocampal mossy fiber-CA3 pathway requires fine-tuned MMP-9 proteolytic activity.

Mechanisms of synaptic plasticity involve proteolytic activity mediated by a complex system of proteases, including members of metalloproteinase (MMP) family. In particular, MMP-9 is critical in LTP maintenance in the Schaffer collateral-CA1 pathway and in the acquisition of hippocampus-dependent memory. Recent studies from this laboratory revealed that in the mossy fiber-CA3 (MF-CA3) projection, where LTP induction and expression are largely presynaptic, MMPs blockade disrupts LTP maintenance and that LTP induction is associated with increased MMP-9 expression. Here we used acute brain slices from MMP-9 knock-out mice and transgenic rats overexpressing MMP-9 to determine how manipulations in endogenous MMP-9 affect LTP in the MF-CA3 projection. Both types of transgenic models showed a normal basal synaptic transmission and short-term plasticity. Interestingly, the maintenance of LTP induced in slices from knock-out mice and overexpressing rats was nearly abolished. However, in the presence of active MMP-9, a gradual fEPSP autopotentiation was observed and tetanization evoked a marked LTP in knock-out mice. Additionally, in MMP-9-treated slices from wild-type mice, fEPSP autopotentiation also occurred and partially occluded LTP. This indicates that exogenous protease can restore LTP in null mice whereas in the wild-type, MMP-9 excess impairs LTP. We expected that LTP maintenance in transgenic rats could be re-established by a partial MMP blockade but non-saturating concentrations of MMP inhibitor were ineffective. In conclusion, we demonstrate that LTP maintenance in MF-CA3 pathway requires fine-tuned MMP-9 activity and raises the possibility that altered MMP-9 level might be detrimental for cognitive processes as observed in some neuropathologies.

Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability.

The exact function of the adult brain neurogenesis remains elusive, although it has been suggested to play a role in learning and memory processes. In our studies, we employed cyclin D2 gene knockout (cD2 KO) mice showing impaired neurogenesis as well as decreased hippocampal size. However, irrespectively of the genetic background of cD2 KO mice, this phenotype resulted in neither deficits in the hippocampal-dependent learning ability nor the memory formation. In the present study, cD2 KO mice and control littermates were subjected to hippocampal-dependent behavioral tests with little or no learning component. The knockout mice showed significant impairment in such species-typical behaviors as nest construction, digging, and marble burying. They were building none or poorer nests, digging less robustly, and burying fewer marbles than control mice. Such impairments were previously described, e.g., in animals with hippocampal lesions. Moreover, cD2 KO animals were also more active in the open field and automated motility chamber as well as showed increased explorative behavior in IntelliCage. Both increased motility and explorative behaviors were previously observed in hippocampally lesioned animals. Finally, cD2 KO mice showed normal sucrose preference, however starting from the second exposure to the sweetened solution, while control animals displayed a strong preference immediately. Presented results suggest that either morphological abnormalities of the hippocampal formation or adult brain neurogenesis impairment (or both) alter hippocampal-dependent behaviors of mutant mice without influencing learning abilities. These results may also suggest that adult brain neurogenesis is involved in species-typical behaviors.

Influence of vitamins C and E on cytotoxic activity of adriamycin in chosen cell cultures.

Influence of different concentrations of ascorbic acid (vitamin C) and dl-alpha-tocopherol acetate (vitamin E) on in vitro cytotoxic adriamycin activity, in: embryonic human fibroblasts (CLV102), human melanoma cells (ME18) and adriamycin-resistant subline cells (ME18/R), was studied. IC50 value for each compound (compound concentration in the culture medium, for which 50% of cells survive) was determined. Cells' survival after the used agent was examined with trypan blue test. The relationship between different concentrations of vitamin C and toxicity of adriamycin, used at appropriate IC50 concentrations, was expressed for all the examined cells as their survival decrease, being in direct proportion to the concentration increase of this vitamin in the medium. In the case of influence of vitamin E on adriamycin cytotoxicity, the protective effect of this vitamin was observed in the concentration range: from 5 to 300 microg/ml (p < or = 0.0001), as an increase of the examined cell survival for ME18, ME18/R as well as for CLV102, comparing to the control (p=0.05) without this vitamin. Parallelly, a statistically significant survival decrease was observed, if the concentration of vitamin E in the culture medium exceeded 500 microg/ml. Received results showed different, in defined concentration range, effects of the vitamin C or vitamin E activity for adriamycin cytotoxicity. These effects were similar for all the examined cells.