MODULE SUPPLEMENT: NEUROLOGICAL SYSTEM
What is Brain Damaging?

What has been implicated as brain damaging?

Calcium has been implicated in the damage that occurs in the aging brain (Gibson & Peterson, 1987; Mattson, 1999; other). Many aspects of calcium homeostasis change with aging although the numerous calcium compartments complicate studies of altered regulation. However, as noted above, excess calcium can be toxic to cells, often leading to excess oxidative stress.

Another important area of study relates to the accumulation of amyloid. Amyloid is really a generic term for proteinaceous fibrillary deposits with certain properties (Timiras, 1994). One form, amyloid B-peptide (AB), is found to form insoluble aggregates in the brain and vasculature as individuals age. These are called plaques when large, and are especially prominent in persons with Alzheimer's disease (Haas & Baumeister, 1999; Mattson, 1999). AB is cleaved from a larger B-amyloid precursor protein (APP) and can be found in two forms, one that is not associated with neuronal degeneration and one that is (Toxic AB).

A great deal of research has been carried out to elucidate why excessive amounts of the toxic AB is produced in certain individuals. Three genetic mutations, one that encodes for the B-Amyloid precursor protein, and two that encode for either presenilin 1 or 2, have been found to be associated with Alzheimer's disease (Haass & Baumeister, 1999).

For more information concerning the influence of these mutations on the cleavage of the precursor protein and the production of AB, see: R & D Systems--Mini-Review: Alzheimer's Disease. (Note: This link will open in a new browser window which you can close to return here.)

In addition, the apoE4 allele has also been found to be a risk factor (Levy-Lahad, Tsung, & Bird, 1998). However, many cases are not easily explained at the current time. And some individuals die with evidence of plaques and tangles who were never identified as being demented. Thus more research is needed to further our understanding of the various mechanisms underlying brain aging and pathology.