Present and Future Pharmacological Treatment of Alzheimers Disease

There is not as yet a pharmacological treatment addressing the causative factors of the disease, capable of preventing or arresting the devastating neuropathology of AD and its clinical consequences. Much of the current pharmacological approaches are mainly directed at corrected neurotransmit-ter-specific deficiencies. This approach has been based on the early realization that AD is accompanied by a preferential loss of cholinergic markers in the cerebral cortex. More recently, NMDA receptor...

Markers of Glutamate Neurotransmission in Alzheimers Disease

Pyramidal neuron loss is a feature of Alzheimer's disease (AD) (Francis et al., 1993 Morrison & Hof, 1997 Neary et al., 1986) and this can be seen reflected as atrophy and in loss of wet weight and total protein of cortical regions by gravimetric analysis (Najlerahim & Bowen, 1988a, 1988b). Glutamatergic neurons account for many of the neurons lost in the cerebral cortex and hippocampus in AD (Greenamyre, Maragos, Albin, Penney, & Young, 1988 Morrison & Hof). Accompanying loss of...

Natural History of Alzheimers Disease

The natural history of AD can be broadly considered as a presymptomatic stage during which a number of pathological events take place over many years, an early symptomatic or prodromal stage (aMCI) with cognitive and at times neuropsychiatric manifestations, and symptomatic mild, moderate, and severe stages. Hoping for reversibility of pathological changes, the early stages of AD can be targeted for disease modification, requiring different trial designs and outcomes (Table 1). Disease...

References

A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., et al. (2003). Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression A randomized controlled trial. The Journal of the American Medical Association, 289, 2819-2826. Bi, X., Baudry, M., Liu, J., Yao, Y., Fu, L., Brucher, F., et al. (2004). Inhibition of ger-anylgeranylation mediates the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors on microglia. The Journal of...

Existing Drugs Discovered or Identified to Possess Two or More Cotargeted Therapeutic Mechanisms of Action

Rasagiline is an antiparkinson-antialzheimer neuroprotective drug with MAO-B inhibition activity (Youdim, Bar Am, et al., 2005 Youdim, 2006). Since its S isomer, TV1022, is more than a 1000 times less potent as an MAO inhibitor than rasagiline, but still possesses neuroprotective activity, it was suggested that the propargylamine moiety is responsible for the neuroprotective activity seen in both these compounds (Youdim, Bar Am, et al., Zheng, Gal, et al., 2005 Zheng, Weiner, et al., 2005...