Copernicus revisited: amyloid beta in Alzheimer's disease.
The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.
Joseph
J
J
USDA-HNRC at Tufts University, 711 Washington Street, Boston, Massachusetts 02111, USA. jjoseph@hnrc.tufts.edu
Shukitt-Hale
B
B
Denisova
N A
NA
Martin
A
A
Perry
G
G
Smith
M A
MA
D000367:Age Factors; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001526:Behavioral Symptoms / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016207:Cytokines; D008563:Membrane Lipids