Does Physical Exercise Modify the Pathophysiology of Alzheimer's Disease in Older Persons?

Physical exercise is well known for its benefits on brain health. However, the mechanisms through which these benefits occur remain discussed, especially in the context of cognitive conditions such as Alzheimer's disease. The present short review summarizes the findings of interventional studies that examined the effects of exercise training on the specific and non-specific biomarkers of Alzheimer's disease. Controlled exercise intervention studies published in the English language were selected if they assessed the effects of a physical exercise intervention of at least 2 weeks in middle-aged or older adults on one of the following biomarkers measured either in the brain, the cerebrospinal fluid or the blood: beta-amyloid, tau, neurofilament light chain, and glial fibrillary acidic protein. Overall, there was no strong evidence of significant effects of exercise interventions on any of the selected biomarkers. However, in specific populations, such as women with obesity, pre-diabetes, or depression, favorable changes in blood beta-amyloid concentrations were reported. Further benefits on cerebrospinal fluid beta-amyloid were also demonstrated in APOE-ε4 allele carriers with Alzheimer's disease. In conclusion, the current evidence suggests that physical exercise does not modulate the pathophysiology of Alzheimer's disease in the overall population of middle-aged and older adults. Nonetheless, some specific populations, such as women with metabolic disorders and Alzheimer's disease patients with APOE-ε4 genotype, seem to be favorably affected. Further studies, including long follow-ups, large sample sizes, and concomitantly assessing the effects of other factors such as sedentary behavior and diet, are required to bring further evidence to the field.

Partial characterization of the gene encoding myoadenylate deaminase from the teleost fish Platichthys flesus.

AMP-deaminase (AMPD, EC 3.5.4.6), which catalyzes the irreversible hydrolytic deamination of AMP to IMP and ammonia, is an important energy-related enzyme. The partial genomic sequence of the gene encoding myoadenylate deaminase (AMPD1) from the teleost fish Platichthys flesus was determined. The amino acid sequence of P. flesus AMPD1 shows 82% homology with that of the teleost fish Danio rerio. Comparison of genomic sequences of P. flesus and Rattus norvegicus reveals a high degree of conservation of both sequence and structural organization. A phylogenetic analysis of AMPD sequences shows that bony fish and mammalian AMPD1s arise by duplication of a common primordial gene.

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases ? Data from the MAPT Study.

BACKGROUND: No study has tried to distinguish subjects that become frail due to diseases (frailty related to diseases) or in the absence of specific medical events; in this latter case, it is possible that aging process would act as the main frailty driver (age-related frailty). OBJECTIVES: To classify subjects according to the origin of physical frailty: age-related frailty, frailty related to diseases, frailty of uncertain origin, and to compare their clinical characteristics. MATERIALS AND METHODS: We performed a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 195 subjects ≥70 years non-frail at baseline who became frail during a 5-year follow-up (mean age 77.8 years ± 4.7; 70% female). Physical frailty was defined as presenting ≥3 of the 5 Fried criteria: weight loss, exhaustion, weakness, slowness, low physical activity. Clinical files were independently reviewed by two different clinicians using a standardized assessment method in order to classify subjects as: "age-related frailty", "frailty related to diseases" or "frailty of uncertain origin". Inconsistencies among the two raters and cases of uncertain frailty were further assessed by two other experienced clinicians. RESULTS: From the 195 included subjects, 82 (42%) were classified as age-related frailty, 53 (27%) as frailty related to diseases, and 60 (31%) as frailty of uncertain origin. Patients who became frail due to diseases did not differ from the others groups in terms of functional, cognitive, psychological status and age at baseline, however they presented a higher burden of comorbidity as measured by the Cumulative Illness Rating Scale (CIRS) (8.20 ± 2.69; vs 6.22 ± 2.02 frailty of uncertain origin; vs. 3.25 ± 1.65 age-related frailty). Time to incident frailty (23.4 months ± 12.1 vs. 39.2 ± 19.3 months) and time spent in a pre-frailty condition (17.1 ± 11.4 vs 26.6 ± 16.6 months) were shorter in the group of frailty related to diseases compared to age-related frailty. Orthopedic diseases (n=14, 26%) were the most common pathologies leading to frailty related to diseases, followed by cardiovascular diseases (n=9, 17%) and neurological diseases (n = 8, 15%). CONCLUSION: People classified as age-related frailty and frailty related to diseases presented different frailty-associated indicators. Future research should target the underlying biological cascades leading to these two frailty classifications, since they could ask for distinct strategies of prevention and management.

Yeast phenylalanyl-tRNA synthetase. Properties of the histidyl residues.

Reactivity of the histidyl groups of yeast phenylalanyl-tRNA synthetase was studied in the absence or presence of substrates. In the absence of substrates about 10 histidine residues were found to react with similar kinetic constants. Phenylalanine at 10(-3) M was found to protect two histidyl residues; increasing the amino acid concentration to 5 . 10(-3) M resulted in the protection of two more histidyl groups. tRNAPhe did not afford any protection to histidine residues, but acylated phenylalanyl-tRNA (Phe-tRNAPhe) protected two of the four histidyl groups already protected by phenylalanine. These results suggest the existence of two different sets of accepting sites for phenylalanine: one specific for the free amino acid, the other one specific for the amino acid linked to the tRNA, but being accessible to free phenylalanine, with a somewhat lower binding constant, ATP was found to mask around four histidyl residues against diethylpyrocarbonate modification. By photoirradiation of enzyme-phenylalanine complex in the presence of rose bengale, a significant amount of amino acid was bound to the alpha subunit (Mr = 73 000) of phenylalanyl-tRNA synthetase, confirming that the amino acid binding site is located on this subunit, as previously suggested by modification of thiol groups. Upon irradiation of an enzyme-tRNA complex, almost no covalent binding of tRNA occurred during enzyme inactivation, suggesting that the histidyl residues involved in the enzymic activity are not required for tRNA binding.

Regulatory properties of pigeon heart muscle AMP deaminase.

The kinetic and regulatory properties of purified pigeon heart muscle AMP deaminase were investigated. In the presence of 100 mM potassium chloride, the enzyme exhibited a slightly sigmoidal type of kinetics. Addition of ATP to the incubation medium changed the reaction rate versus substrate concentration plot into a hyperbolic one, and caused a decrease of the half-saturation constant (S0.5). ADP presence caused the change of both the S0.5 and Vmax parameters, exerting either an activating or inhibitory effect, depending upon the substrate concentration. Orthophosphate inhibited the enzyme at all substrate concentrations, increasing the value of the S0.5 parameter. In the presence of ATP, ADP and orthophosphate, added to the incubation medium at approximately physiological concentrations, pigeon heart AMP deaminase still seems to preserve its activated form. Active long chain fatty acids clearly inhibited enzyme activity even at micromolar concentrations. Interpretation of the kinetic data in terms of the allosteric theory of Monod et al. (1965, J. Mol. Biol. 12, 88-118) indicates that heart muscle AMP deaminase may operate as a functionally active dimer.

Purification and characterization of a new DNA polymerase modulator from the hyperthermophilic archaeon Thermococcus fumicolans.

During purification of the native alpha-like DNA polymerase from the hyperthermophilic euryarchaeote Thermococcus fumicolans, two activity peaks were detected after cation-exchange chromatography. One of the peaks (Ppol) was identified as the T. fumicolans DNA polymerase and the second peak (Pf) was shown to contain a factor which increased the DNA polymerase activity over 70-fold when tested with activated calf thymus DNA as substrate. The factor also stimulated nucleotide incorporation when using primed lambda DNA as substrate (approximately 8-fold), while inducing a very large decrease in the turnover rate of the enzyme. The factor, therefore, maximizes the ability of the DNA polymerase to synthesize small fragments, which is compatible with DNA repair or lagging strand DNA replication.

The CYTOS biological experiments carried out on the Soviet orbital station Salyut 6.

Two biological experiments (CYTOS programme) were performed aboard the Soviet orbital Station Salyut 6. For these experiments we have developed several original devices. In this paper we give the technical characteristics of this specialized hardware and the experimental methods used to carry out these experiments.

[Knowledge, opinions and tobacco consumption in a French faculty of medicine]. / Connaissances, opinions et consommation de tabac au sein d'une faculté de médecine française.

OBJECTIVE: Tobacco consumption among French physicians is regularly followed-up and well-known; however, there is little information concerning the smoking habits of medical students even though they are the physicians of the future. How do they behave? Do they smoke? More or less than the other populations of the same age? METHOD: All the students of a Parisian medical school were surveyed with a self-questionnaire completed and collected just before the exams at the end of the year. The questionnaire incorporated both past and present smoking habits and also the students' knowledge and opinions on tobacco consumption. RESULTS: A total of 681 students replied. More than one-third were smokers (34.6%) among which 21.0% smoked every day and 13.6% smoked occasionally. Gender had no influence on prevalence rate and both men and women smoked a comparable number of cigarettes per day (males 12.0 cig/day, females 10.4 cig/day). Eleven percent were former smokers and 68.4% would like to quit. Nearly 100% believed that cigarette smoke can bother others and 75% felt they were exemplary figures for others on the subject of tobacco use. Finally, two-thirds of the students smoked light cigarettes. CONCLUSION: The smoking habits of medical students are similar to those of the general population of the same age. It is necessary to develop specific prevention programs for medical students because they will play an important public health role in the future in reducing the prevalence of tobacco consumption in France.

Preliminary results of Cytos 2 experiment.

Cytos 2 experiment, carried out during the French-Soviet manned flight (July 1982), has studied the antibiotics sensitivity of bacteria cultivated in vitro during the orbital flight. The results show an increase of the antibiotics resistance and a larger thickness of the cellular envelope for the inflight cells. The increase of antibiotics resistance can be related to a stimulating effect of space on the cell growth rate or to changes of the cellular envelope structure.

Activation of trout gill AMP deaminase by an endogenous proteinase--I. Effects on the regulatory properties of the enzyme.

Some regulatory properties of trout gill AMP deaminase were determined in crude extracts, before or after modification of the enzyme by the endogenous proteinase. After proteolysis, the optimal concentrations for activation by sodium and potassium were shifted from 10 to 75 mM, resulting in a large increase of enzyme activity near the physiological potassium concentration. This activation was shown to be the consequence of a much lower sensitivity of AMP deaminase to inhibition by increasing ionic strength. The modified enzyme was also less sensitive to modifications of pH and to inhibition by physiological concentrations of inorganic phosphate. When all these modifications were considered, limited proteolysis of gill AMP deaminase resulted in a 40 times increase of enzyme activity under in vivo conditions.

Activation of trout gill AMP deaminase by an endogenous proteinase--II. Modification of the properties of the enzyme during starvation, pollution and salinity changes.

The relative amount of modified AMP deaminase has been determined by taking advantage of the different effects of monovalent cations on the two enzymatic forms. When trout were subjected to different environmental perturbations (starvation, pollution of the water by a pesticide, transfer to sea water or reverse transfer to fresh water), modified AMP deaminase could be detected in the gill extracts. Depending on the nature of the stress and the period of experimentation, 8 to 100% of the enzyme had been modified by limited proteolysis. As a consequence of the much higher activity of the proteolyzed AMP deaminase form, a 2 to 12 times increase of the intracellular AMP deaminase activity could be expected. At the same time, limited proteolysis will modify the regulatory properties of the enzyme, since it can be estimated that 50 to 100% of the enzyme activity expressed in the cell will be an AMP deaminase form less sensitive to inhibition by inorganic phosphate and ionic strength, and to variations of the intracellular pH. Limited proteolysis will result in increased AMP deaminase activity under conditions of increased energy demand, where the concentration of inorganic phosphate is dramatically increased. The consequence should be stabilization of the adenylate energy charge.

Activation of trout gill AMP deaminase by an endogenous proteinase--III. Comparative studies on the gill AMP deaminase from different fresh water and sea water teleosts.

The effects of monovalent cations and inorganic phosphate, on gill AMP deaminase, were compared in different fresh water and sea water stenohaline and euryhaline Teleosts. Generally, sea water species displayed a lower sensitivity to these effectors than fresh water species. During salinity changes, the sensitivity of gill AMP deaminase to cations and phosphate were modified proportionally to the tolerance of a given species to variations of environmental salinity. In particular, these parameters were modified in the weak euryhaline, Salmo gairdneri, but not in the real euryhaline, Anguilla anguilla. In sea water adapted trout, the appearance of a modified AMP deaminase form, with similar properties to that found in sea water species, is suggested. When compared with the conclusions from the preceeding papers [Raffin (1986) Comp. Biochem. Physiol. 85B, 157-162; 85B, 163-171], the results suggest that modification of gill AMP deaminase by limited proteolysis should be a rather general adaptation mechanism to stress.

[Cytoarchitecture of the principle diencephalic visual centers in the embryo and the chicken Gallus domesticus L. Experimental study]. / La cytoarchitecture des principaux centres visuels diencéphaliques de l'embryon et du poussin de Gallus domesticus L. Etude expérimentale

The effects of the bilateral removal of the optic vesicle on the cytoarchitectonics of the main diencephalic visual centres of Gallus domesticus L. embryos and chicken have been studied from the 10th, day of incubation until the 15th, day after hatching. - Without afferent optic pathways there is no significnat change in cellular components of nucleus lateralis anterior, nucleus geniculatus lateralis ventralis, nucleus griseus tectalis, nucleus rotundus and nucleus pretectalis principalis. When these centres have specific organization, one may observe a spatial distribution of neurons different from that of unoperated chickens. - Whereas the nucleus ectomamillaris disappears early, the nucleus superficialis synencephali is not differentiated. the nucleus geniculatus lateralis dorsalis, reduced in size, shows an alternation of cell constitution even if cytoarchitectonics appears to be similar to that of unoperated chickens. A comparison of these results with those on tectum opticum by authors brings up the question of the exact nature of retino-thalamic connections and of their morphogenetic role. If morphogenetic influence appears to be certain on some structures it seems to be limited on others.

AMP deaminase from dogfish erythrocytes: purification and some properties.

The AMP deaminase from erythrocytes from the dogfish, Scyliorhinus caniculus, L., was purified by chromatography on cellulose-phosphate and DEAE-cellulose. The 1300-fold purified enzyme was highly unstable. At low substrate concentrations, a sharp pH optimum was found at pH 6.7. At higher substrate concentrations, the highest activity was found between pH 6.8 and 7.2. The substrate saturation curve was hyperbolic in the presence of monovalent cations. The binding of inorganic phosphate showed cooperativity. Overall the kinetic properties of AMP deaminase from erythrocytes from dogfish are very similar to that described for other species.

AMP deaminase from the gill of the mullet Chelon labrosus R.: purification and effects of pH, phosphate and monovalent cations.

The AMP deaminase from the gill of Chelon labrosus was purified about 250-fold by chromatography on cellulose-phosphate. At low and high substrate concentration, a sharp pH optimum was found between pH 6.7 and 6.9. The enzyme was found to be relatively insensitive to physiological concentrations of inorganic phosphate. Na+ and K+ were activators of gill AMP deaminase, Na+ being the most efficient. Effects of possible changes in the intracellular concentrations of these cations on enzyme activity are discussed.

AMP deaminase from the gill of Salmo gairdnerii Richardson: effects of anions, cations and buffers.

The AMP deaminase isoenzymes from trout gill were activated by sodium and potassium, sodium being the most efficient. The optimal concentration for activation was 30-50 mM. The enzyme was sensitive to ionic strength, and imidazole was an inhibitor at concentrations higher than 25 mM. A possible regulation of gill AMP deaminase by intracellular imidazole buffers is discussed. AMP deaminase activity was tested in the presence of physiological concentrations of sodium and potassium. When the concentration of one of these cations was varied around its physiological concentration, the enzyme activity was relatively stable, indicating that the intracellular AMP deaminase activity would be insensitive to changes in the concentrations of monovalent cations. The effects of the sodium salts of different inorganic and organic anions were tested. Except chloride and gluconate, all were inhibitors of gill AMP deaminase.