ApoE4, a-beta, and Alzheimer's disease susceptibility
Professor Dennis Selkoe discusses the degree to which the ApoE4 gene is associated with early onset Alzheimer's disease.
One of the most important risk factors for Alzheimerâ€™s [disease] is this gene called ApoE4. If one has one or even two copies â€“ two copies means one from Mom and one from Dad â€“ you are predisposed to having a higher likelihood of Alzheimerâ€™s [disease]. But, importantly, that tendency to Alzheimerâ€™s [disease] wonâ€™t really show itself until you are in your sixties or your fifties, and it is true that a-beta levels may build up in the brain far earlier than that, maybe in the twenties or thirties or forties. But there is little evidence that it builds up already at five or seven, or ten, or two years old, etc. So, while it is true that ApoE4 carriers will eventually build up too much a-beta, and theyâ€™ll do it much earlier than the typical Alzheimerâ€™s [disease] patient, who wonâ€™t start building it up until 50 or 60, theyâ€™ll do it earlier than that. But I donâ€™t have evidence from anything I know that theyâ€™ll build up a-beta per se already at two or five or ten. They may build it up, but it may be later than that. What I do know, though, is that ApoE4 is a complex and tricky protein. It can cause changes in cortical thickness and cortical health independent of its acceleration of a-beta buildup, so I am aware of studies in ApoE4 carriers, even by functional MRI or MRI imaging, that ApoE4 inheritance in a person will change cortical thickness and that kind of thing. But I am not aware that, if cortical thickness is altered in early life, that can be attributed to the a-beta problem coming from ApoE4. That has been a bit of a debate in the field. Itâ€™s clear that ApoE4, compared to the other two ApoEs (E3 and E2) will cause the brain to develop somewhat differently and cause the thickness of the cortex or certain neuronal connections to be different, and science hasnâ€™t figured out yet whether thatâ€™s a separate, effective ApoE4 [rather] than itâ€™s acceleration of a-beta buildup. In my view, I donâ€™t think we have enough information to say that everything that goes wrong in the nervous system with people who have ApoE4 can be attributed to a-beta, to that part of the problem. I think it may be true, true, and unrelated.
apoe4, apoprotein, e4, e3, e2, a-beta, abeta, early, late, onset, alzheimer, dennis, selkoe
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2190. Late-onset genes for Alzheimer's disease
Professor Donna Wilcock discusses the late-onset gene for Alzheimer's disease, ApoE4, which increases the risk of developing the disease.
2139. Cell death and a-beta levels
Professor Dennis Selkoe discusses the largely linear relationship between a-beta and cell death in the brain.
2135. APP - amyloid clearance and production
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.
2137. Amyloid plaques - rarely found in childhood
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.
2189. Late-onset Alzheimer's disease
Professor Donna Wilcock discusses late-onset Alzheimer's disease, which involves the clearance and/or production of the amyloid beta protein.
2227. Alzheimer's disease
An overview of Alzheimer's disease-related content on Genes to Cognition Online.
2136. Amyloid beta causing forgetfulness
Professor Dennis Selkoe discusses an experiment by his group, which found that a-beta oligomers temporarily injected into rats' brains caused temporary forgetfulness.
2141. Glutamate uptake decreased in Alzheimer's disease
Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.
2140. Cells - a-beta inhibits long-term potentiation
Professor Dennis Selkoe notes amyloid beta oligomers are very potent inhibitors of long-term potentiation (LTP) and can 'short circuit' synapses in the hippocampus.
2142. Cells affected in Alzheimer's disease
Professor Dennis Selkoe concludes that neurons are not the only type of cell affected in Alzheimer's disease.