Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder affecting millions of people. Synaptic dysfunction and physical loss of synapses are responsible for memory impairments in AD. The molecular mechanisms responsible for synaptic loss in AD are not understood. The main risk factor for sporadic AD (SAD) is advanced age. Missense mutations in presenilin (PS) proteins and in amyloid precursor protein (APP) are responsible for majority of rare familial AD (FAD) cases. Increased production of A 42 amyloidogenic peptide occurs in SAD and FAD. Synaptotoxic effects of A 42 may be linked to synaptic loss in AD. FAD mutations in PS proteins disrupt endoplasmic reticulum (ER) calcium (Ca 2+ ) leak function of PSs and result in increased Ca 2+ levels in neuronal ER. Similar increases in neuronal ER Ca 2+ levels occur in aging neurons. Increased neuronal ER Ca 2+ levels lead to a compensatory upregulation of ER Ca 2+ release channels, the ryanodine receptors (RyanR), and downregulation of the synaptic store-operated Ca 2+ entry (SOC) pathway. In this review we propose a hypothesis that excessive Ca 2+ release from the ER and insufficient SOC Ca 2+ entry lead to destabilization and eventual elimination of mature mushroom spines in PS-FAD neurons and in aging SAD neurons. The proposed Ca 2+ -dependent spine destabilization mechanism may act in parallel or synergistically with A 42 synaptotoxicity mechanisms. The proposed model may help to establish a cause-and-effect connection between abnormal Ca 2+ and amyloid homeostasis and synaptic loss in AD.

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High and low rates of very-low-density-lipoprotein triacylglycerol release from the perfused rat liver were achieved by using livers taken respectively from animals that had been given fructose for 48h or from animals that had been starved for 18h. 2. The higher rates of very-low-density-lipoprotein triacylglycerol release by the livers of the fructose-fed rats were associated with higher rates of very-low-density-lipoprotein protein release. 3. When the livers were perfused in the presence of [3H]leucine, radioactivity was incorporated into the very-low-density-lipoprotein apoproteins. The higher rates of very-low-density-lipoprotein triacylgycerol and protein release by the livers of fructose-fed rats were associated with a greater total incorporation of radioactivity into those apoproteins that entered the running gel during polyacrylamide-gel electrophoresis. However, the distribution of radioactivity among the various apoproteins was not significantly changed by the dietary treatments used.

editorialThe "Theory and methodology" section deals with the issues of international and trans-disciplinary cooperation in contemporary psychology. The paper by Irina A. Мironenko analyses integrative and isolationist tendencies in contemporary Russian psychological science. Lev A. Zaks thoroughly discusses the ways psychology and cultural studies cooperate and the problems they face; an agenda first proposed by L.S. Vygotsky in his early work.

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