There are a number of ways in which a clinical diagnosis of dementia of the Alzheimer type can be made – the application of clinical criteria is the commonest but ancillary techniques such as neuroima

Clinical Diagnosis of Alzheimer's Disease

Lipids of nervous tissue: composition and metabolism.

Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss of myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelination and myelin balloon figures. The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve conduction velocity, muscle strength, sensory discrimination, autonomic responses, and endoneurial blood flow. The age-related decline in nerve regeneration after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is delayed in aged animals, with myelin remnants accumulated in the macrophages being larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic factors secreted by reactive Schwann cells and target organs are lower in older subjects than they are in younger subjects. The rate of axonal regeneration becomes slower and the density of regenerating axons decrease in aged animals. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinnervation and functional restitution. These age-related changes are not linearly progressive with age; the capabilities for axonal regeneration and reinnervation are maintained throughout life, but tend to be delayed and less effective with aging.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1529-8027.2000.00026.x

Influence of aging on peripheral nerve function and regeneration.

Sarcopenia is a loss of muscle mass and function in the elderly that reduces mobility, diminishes quality of life, and can lead to fall-related injuries, which require costly hospitalization and ex...

/pdf/sarcopenia-aging-related-loss-of-muscle-mass-and-function-2u9nyjfrxt.pdf

Sarcopenia: Aging-Related Loss of Muscle Mass and Function.

Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.

/pdf/regulation-of-pyruvate-metabolism-and-human-disease-2vflael6v2.pdf

Regulation of pyruvate metabolism and human disease.

— The calcium-dependent incorporation of choline, ethanolamine and L-serine into the phospholipids of isolated rat brain microsomes has been studied in vitro, and various properties of the incorporation have have been examined. The optimum pH for the incorporation of each base was found to vary inversely with the Ca2- concentration. Conversely, the optimal Ca2 + concentration for the exchange of the bases increased with decreasing pH values. The enzymic system for the incorporation of ethanolamine appeared to be saturated by two substrate concentrations, i.e. 0-2 and 1-7-2-0 mM. At low ethanolamine concentration (0-2 mM] much less incorporation of the base occurred into the alkenylacyl- and alkylacyl-derivatives of ethanolamine phosphoglycerides compared to that into the diacyl species, whereas the difference becomes smaller at a high substrate concentration (1-7 mM). At pH 81 and 2 mM-Ca2+ the apparent Km of ethanolamine at low substrate concentration was 80 × 10-5 M, and this value increased to 16-2 × 10-4.viat 10mM-Ca2+ concentration. At similar pH the Km values for choline and L-serine were 5.88 × 10-4M and 40 × 10-4 M at 2 mM- and 10mM-Ca2 + concentrations, respectively. The properties of the enzyme system show differences for the three substrates when various factors are changed during incubation. These and other results indicate that more than one enzyme is probably involved in the Ca2+-medialed exchange of nitrogenous bases.

Properties and function of the calcium-dependent incorporation of choline, ethanolamine and serine into the phospholipids of isolated rat brain microsomes.

Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease

The biosynthesis of choline and ethanolamine phosphoglycerides was tested in vivo in different brain areas of the rat during aging. Mixtures of [2−3H] glycerol and [Me-14C] choline or [2-3H] glycerol and [2-14H] ethanolamine were injected into lateral ventricle of the brain as lipid precursors and their incorporation into corresponding phospholipid was examined. A significant decrease of synthesis of both phosphoglycerides takes place in cerebral cortex and in the striatum, and is already apparent at 9 months of age with no further decrease or change therafter. No significant change takes place in the cerebellum. The unchanged absorption of injected water-soluble precursors, together with the lack of any significant change of phospholipid/protein ratio in all examined brain areas, suggests that the incorporation of both glycerol and nitrogen bases are affected by aging.

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging

Both low and high platelet MAO-B (pMAO-B) activity is considered an indicator of increased vulnerability in psychopathology. How the activity of this peripheral enzyme can be linked with the sophisticated functions of the central nervous system (CNS) is not clear; in man, evidence exists that the genetic mechanisms determining the size or capacity of the central serotonin system are common to platelet and brain MAO. In the present study pMAO- B activity was evaluated in demented patients suffering from early- onset Alzheimer’s disease (AD), late- onset Alzheimer’s disease (SDAT), vascular dementia (VD), and controls. In these dementia categories, the relationship between pMAO- B activity and clinical features, and between pMAO- B activity and cerebrospinal fluid (CSF) monoamine metabolites (3-methoxy-4-hydroxyphenyl-glycol, MHPG; 5-hydroxy-in-doleacetic acid, 5-HIAA; homovanillic acid, HVA) was also investigated. pMAO-B activity was significantly higher in SDAT patients, compared to controls and AD. Age, as covariate, failed to show any significant effect, and no association was found between pMAO-B activity and CSF monoamine metabolites. The correlation analysis between pMAO-B and neuropsychological scores showed a highly significant positive relationship with GBS- emotional impairment (N=40, r=0.72, p<0.01 in the SDAT group. This result suggests the importance of platelet MAO- B activity as biological marker also in old- age dementias, namely senile dementia of Alzheimer type, where the increased activity of this enzyme might constitute a marker for vulnerability toward behavioural disturbance, i.e., emotional deterioration. (Aging Clin. Exp. Res. 6: 201–207, 1994)

Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders.

[3H]Palmitic acid and [14C]arachidonic acid were injected together into the cerebral ventricle of 4-month and 24-month-old rats. At different time intervals from the injection, the distribution of these fatty acids in the lipids from different brain areas was examined. The fatty acids were rapidly incorporated into the lipids through different mechanisms. The time-specific activity relationship indicate that the utilization of the fatty acid differs according to the different areas and aging decreases the utilization of both the fatty acids. The decline of arachidonic acid incorporation into phospholipids is particularly evident, indicating that aging affects mainly the utilization of polyunsaturated fatty acids.

M. Brunetti

Papers

Properties and function of the calcium-dependent incorporation of choline, ethanolamine and serine into the phospholipids of isolated rat brain microsomes.

Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging

Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders.

Turnover of palmitic and arachidonic acids in the phospholipids from different brain areas of adult and aged rats.