Reassessing the amyloid cascade hypothesis of Alzheimer's disease
Pimplikar SW.
Department of Neurosciences,
Lerner Research Institute,
Cleveland Clinic, Cleveland, OH 44195,
United States.
Int J Biochem Cell Biol. 2008 Dec 30.


Since its inception, the amyloid cascade hypothesis has dominated the field of Alzheimer's disease (AD) research and has provided the intellectual framework for therapeutic intervention. Although the details of the hypothesis continue to evolve, its core principle has remained essentially unaltered. It posits that the amyloid-beta peptides, derived from amyloid precursor protein (APP), are the root cause of AD. Substantial genetic and biochemical data support this view, and yet a number of findings also run contrary to its tenets. The presence of familial AD mutations in APP and presenilins, demonstration of Abeta toxicity, and studies in mouse models of AD all support the hypothesis, whereas the presence of Abeta plaques in normal individuals, the uncertain nature of the pathogenic Abeta species, and repeated disappointments with Abeta-centered therapeutic trials are inconsistent with the hypothesis. The current state of knowledge does not prove nor disprove the amyloid hypothesis, but rather points to the need for its reassessment. A view that Abeta is one of the factors, as opposed to the factor, that causes AD is more consistent with the present knowledge, and is more likely to promote comprehensive and effective therapeutic strategies.
Eugenics talk
Private eugenics
'Saviour siblings'
Personal genomics
Psychiatric genetics
Human self-domestication
Selecting potential children
Alzheimer's disease: resources
Transhumanism/Brave New World?
Francis Galton and contemporary eugenics
Gene therapy and performance enhancement
Preimplantation genetics and stem cell therapy
Defining the genetic signature of Alzheimer's Disease

and further reading

BLTC Research
Utopian Surgery?
The Good Drug Guide
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
MDMA: Utopian Pharmacology
Critique of Huxley's Brave New World