ALZHEIMER'S DISEASE (AD)

One popular but clearly refuted concept is that aging is normally associated with a progressive loss of brain nerve cells (neurons) that would account for age-dependent memory losses. The belief that nerve cells in the human brain die throughout adult life arose mainly from invalid cell counting methods (reviewed in Neurosci Biobehav Rev 2002;26:733-41; Progr Brain Res 2002;136:39-65). Declining mental performance with aging is very likely caused by qualitative changes in nerve cells surviving a lifetime. Aging neurons generally tend to exhibit structural changes such as altered cell-to-cell connections known as dendrites and synapses and accumulations of inclusion bodies. Note, however, that progressive nerve cell death is an integral feature of Alzheimer's dementia, but cell death as demonstrable in this disease is not considered normal (physiological) aging.

One misconception that prevailed until recent years is that the brain is incapable of generating new brain cells (neurons) by cellular division. Some areas of the brain (dentate gyrus, olfactory bulb) can generate new neurons. However, it is true that the brain has generally a limited ability to regenerate new functional tissue compared with other organs such as skin, skeletal muscle, and liver.

Using molecular markers (cell cycle markers) that indicate whether cells are about to divide or have just divided, it has become clear that cells of organs with low potential for tissue regeneration (brain, heart muscle, lens of eye) may respond to growth stimuli with appropriate cell division ("mitosis"), but that the two daughter cells generated by the division are unstable and die. Cells undergoing such "post-mitotic cell deaths" are detectable using special cell death markers. The presence of cell cycle markers as a sign of mitosis in tissues such as brain or heart without characterizing the fate of the daughter cells may lead to the false conclusion that the tissue has acquired stable new cells.