Cell death and a-beta levels
Professor Dennis Selkoe discusses the largely linear relationship between a-beta and cell death in the brain.
There is a linear relationship between a-beta build-up and neuronal dysfunction, and ultimately neuronal death. Nowadays in Alzheimerâ€™s disease we are more interested in the subtle dysfunction of a neuron, long before it gives up the ghost. So we donâ€™t even talk or focus as much on neuronal death, although unequivocally that happens in the fullness of time with Alzheimerâ€™s [disease] patients. By and large there is a linear relationship. Itâ€™s not a perfect line; itâ€™s scattered along an axis that goes up diagonally between a-beta amount and age, but within that scatter you can draw a statistically significant relationship. So that happens, for example, and weâ€™ve published some of this work some years ago. It happens with a-beta levels and ApoE4. There is a correlation between ApoE4 genotype and a linear rise in a-beta buildup. The more a-beta you get, you eventually exceed a threshold, and then youâ€™re very likely to have enough a-beta in your brain that these doublets and triplets and quadruplets and perhaps somewhat higher oligomers are going to short circuit nerve cells in the hippocampus and cause synaptic function to decline. So, by and large, itâ€™s a quantitative issue, not a qualitative issue in Alzheimerâ€™s [disease], at least thatâ€™s what we believe right now.
a-beta, abeta, alzheimers, cell, death, neuron, brain, dennis, selkoe
Professor Dennis Selkoe concludes that neurons are not the only type of cell affected in Alzheimer's disease.
An overview of Alzheimer's disease-related content on Genes to Cognition Online.
Professor Dennis Selkoe notes amyloid beta oligomers are very potent inhibitors of long-term potentiation (LTP) and can 'short circuit' synapses in the hippocampus.
Professor Dennis Selkoe discusses the degree to which the ApoE4 gene is associated with early onset Alzheimer's disease.
Professor Dennis Selkoe discusses the age at which plaque-forming a-beta can begin to build up. Children with Down syndrome may have these plaques, otherwise childhood instances are rare.
Professor Dennis Selkoe discusses an experiment by his group, which found that a-beta oligomers temporarily injected into rats' brains caused temporary forgetfulness.
Professor Dennis Selkoe compares the amyloid precursor (or parent) protein to a Bic pen. The clasp part seems to be the bad guy, and is part of a network involving presenilin and ApoE4.
Professor Kenneth Kosik describes senile plaques, an extracellular collection of a-beta protein. It is one of the hallmarks of Alzheimer's disease.
Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.
Professor Dennis Selkoe explains that amyloid beta oligomers - small assemblies of amyloid beta protein associated with Alzheimer's disease - do not cause plaques but prevent them.