Journal of Alzheimer's Disease - Volume 2, issue 2

Authors: Andorn, Anne C. | Kalaria, Rajesh N.

Article Type: Research Article

Abstract: Oxidative stress may have a key pathogenetic role in neurodegenerative diseases including Alzheimer's disease (AD). While there is evidence that some amyloid-β (Aβ) peptides can initiate oxidative stress at micromolar doses, there is also some evidence that oxidative stress increases the concentration of the β-protein precursor (βPP) and the potential for increased formation of the Aβ peptides. The following studies were performed to test the hypothesis that fragments of βPP could be antioxidants and hence that oxidative stress might be an early event in AD. We found that several fragments of βPP, including the Aβ peptides, inhibit ascorbate-stimulated lipid peroxidation …(ASLP) in membrane fragment preparations of postmortem human brain. In contrast, other fragments of βPP enhance ASLP. These data indicate that βPP or fragments of bPP could play a key role in the redox status of cells and that alterations in bPP processing could have profound effects on the cellular response to oxidative stress. Show more

DOI: 10.3233/JAD-2000-2201

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 69-78, 2000

Authors: Pappolla, Miguel A. | Ogden-Epker, Melissa

Article Type: Research Article

DOI: 10.3233/JAD-2000-2202

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 79-82, 2000

Authors: Bush, Ashley I. | Atwood, Craig S. | Goldstein, Lee E. | Huang, Xudong | Rogers, Jack

Article Type: Research Article

DOI: 10.3233/JAD-2000-2203

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 83-84, 2000

Authors: Summers, William K.

Article Type: Research Article

DOI: 10.3233/JAD-2000-2204

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 85-93, 2000

Authors: Samuels, Steven C. | Davis, Kenneth L.

Article Type: Article Commentary

DOI: 10.3233/JAD-2000-2205

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 95-96, 2000

Authors: Chen, Ming | Fernandez, Hugo L.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) has been intensively studied for decades, but why has its common pathological cause remained so enigmatic? Our studies have suggested that plaques and tangles occur spontaneously during aging as a result of a natural decline of energy metabolism and Ca2+ signaling, but not necessarily due to conventional pathogens. This view would lead to an unexpected outcome; that is, natural aging plays a more important role in neurodegeneration than is currently recognized. Does this model over-simplify the disease origin? We know that AD-type neurodegeneration typically occurs at the end stages of life when not only do plaques …and tangles appear, but also many other bodily changes as well (bone loss and skin wrinkling, etc). Neurodegeneration differs from the latter changes mainly by “social” consequences, not by “physiological” origin. If neurodegeneration is a natural event, then why do only some people, but not others, develop AD? Obviously, additional factors are required for neurodegeneration to develop into AD. By comparing current models and ruling out other possibilities, we think that several known “risk factors” most likely play a critical role in the late-onset sporadic AD. These risk factors can exert their effects either by providing the conditions for ailing neurons to die (extended longevity and sedentary lifestyle), or by enhancing the individual's “vulnerability” to natural neurodegeneration (low synapse reserve). In this context, late-onset sporadic AD would be similar to many other age-related conditions where perhaps no single pathogen can be held exclusively responsible for most cases; rather, many risk factors are important to allow the initial defect to turn into clinical diseases. Accordingly, these factors should be the primary targets for AD prevention. Yet, some other AD cases, especially the early-onset ones, may be complicated by the concomitant involvement of other diseases in the brain. Show more

Keywords: Alzheimer, aging, calcium, amyloid, presenilin, osteoporosis, atherosclerosis, Parkinson's

DOI: 10.3233/JAD-2000-2206

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 97-108, 2000

Authors: Mattson, Mark P.

Article Type: Article Commentary

DOI: 10.3233/JAD-2000-2207

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 109-112, 2000

Authors: Price, J.L. | Rubin, E.H. | Morris, J.C.

Article Type: Article Commentary

DOI: 10.3233/JAD-2000-2208

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 113-114, 2000

Authors: Khachaturian, Zaven S.

Article Type: Article Commentary

DOI: 10.3233/JAD-2000-2209

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 115-116, 2000

Authors: Ghanbari, Hossein A.

Article Type: Article Commentary

DOI: 10.3233/JAD-2000-2210

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 117-117, 2000