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Frustrating article. Attempts at communicating biology in popular science are invariably incomplete. Additionally, we must realize that identifying targets is f

by et2o 12y ago

Frustrating article. Attempts at communicating biology in popular science are invariably incomplete. Additionally, we must realize that identifying targets is far different from developing effective drugs for these targets. Scanning the comments: No one really thinks that Tau is responsible anymore. The problem is that we only rather recently realized soluble AB oligomers are the most distal causative agent. T3 diabetes is again a distal effect of the etiologic agent of AD; what causes T3 diabetes? I would encourage anyone who is interested to begin with this paper: http://www.cell.com/abstract/S0092-8674(13)00387-5 http://www.cell.com/abstract/S0092-8674(13)00387-5 (Zhang et al. Cell 2013).

pcrh 12y ago
Tau pathology is the best pathological correlate with Alzheimer's disease. What is often overlooked in the study of Alzheimer's disease is the APOE gene. This comes as three forms, each differing from the other by only a few amino acids. These are called APOE2, APOE3 and APOE4. The most common form is APOE3, APOE2 and APOE4 are each present in about 6-10% of people (heterozygous). People who are homozygous for the APOE2 form almost never get Alzheimer's disease, whereas those who have the APOE4 form have a more than 50% chance of getting Alzheimer's disease before they die. So... there must be a link between the APOE gene and tau... since both are the strongest correlates with the disease, in pathology and genetics, respectively. However, you would be hard pressed to find a study that demonstrated a mechanistic link between these two factors (apart from Alzheimer's disease, of course). As a researcher in the field, I think this is one of the most intriguing aspects. Link to open access review on APOE in Alzheimer's disease: http://dx.doi.org/10.1016/j.neuron.2012.11.020 http://dx.doi.org/10.1016/j.neuron.2012.11.020 Edit: For those interested in a reputable collection of recent reviews on the biology of Alzheimer's disease: http://perspectivesinmedicine.cshlp.org/cgi/collection/the_biology_of_alzheimer_disease http://perspectivesinmedicine.cshlp.org/cgi/collection/the_b...
- cariaso 12y ago
  I've never seen an explanation for why APOE1 is rare to non-existent. I feel like understanding that may give useful clues to the larger Alzheimer's question. Do you have any insight? While the population frequency of heterozgosity for the 2 relevant SNPs * http://snpedia.com/index.php/Rs429358 http://snpedia.com/index.php/Rs429358 * http://snpedia.com/index.php/Rs7412 http://snpedia.com/index.php/Rs7412 is low, but not low enough to justify the near total absence of E1/E1.
  - pcrh 12y ago
    A name is just a name. There are about 20 varieties of apoE, most of which are extremely rare, i.e. found in only a handful of families. ApoE1 is simply rare, and not really relevant to Alzheimer's disease, although it does affect blood cholesterol levels. http://www.ncbi.nlm.nih.gov/pubmed/?term=22859420 http://www.ncbi.nlm.nih.gov/pubmed/?term=22859420
  - pcrh 12y ago
    By the way, I see you maintain SNPedia, thanks! The apoE1 snp is Rs121918394

by et2o 12y ago

pcrh 12y ago

Tau pathology is the best pathological correlate with Alzheimer's disease. What is often overlooked in the study of Alzheimer's disease is the APOE gene. This comes as three forms, each differing from the other by only a few amino acids. These are called APOE2, APOE3 and APOE4. The most common form is APOE3, APOE2 and APOE4 are each present in about 6-10% of people (heterozygous). People who are homozygous for the APOE2 form almost never get Alzheimer's disease, whereas those who have the APOE4 form have a more than 50% chance of getting Alzheimer's disease before they die. So... there must be a link between the APOE gene and tau... since both are the strongest correlates with the disease, in pathology and genetics, respectively. However, you would be hard pressed to find a study that demonstrated a mechanistic link between these two factors (apart from Alzheimer's disease, of course). As a researcher in the field, I think this is one of the most intriguing aspects. Link to open access review on APOE in Alzheimer's disease: http://dx.doi.org/10.1016/j.neuron.2012.11.020 http://dx.doi.org/10.1016/j.neuron.2012.11.020 Edit: For those interested in a reputable collection of recent reviews on the biology of Alzheimer's disease: http://perspectivesinmedicine.cshlp.org/cgi/collection/the_biology_of_alzheimer_disease http://perspectivesinmedicine.cshlp.org/cgi/collection/the_b...

cariaso 12y ago
I've never seen an explanation for why APOE1 is rare to non-existent. I feel like understanding that may give useful clues to the larger Alzheimer's question. Do you have any insight? While the population frequency of heterozgosity for the 2 relevant SNPs * http://snpedia.com/index.php/Rs429358 http://snpedia.com/index.php/Rs429358 * http://snpedia.com/index.php/Rs7412 http://snpedia.com/index.php/Rs7412 is low, but not low enough to justify the near total absence of E1/E1.
- pcrh 12y ago
  A name is just a name. There are about 20 varieties of apoE, most of which are extremely rare, i.e. found in only a handful of families. ApoE1 is simply rare, and not really relevant to Alzheimer's disease, although it does affect blood cholesterol levels. http://www.ncbi.nlm.nih.gov/pubmed/?term=22859420 http://www.ncbi.nlm.nih.gov/pubmed/?term=22859420
- pcrh 12y ago
  By the way, I see you maintain SNPedia, thanks! The apoE1 snp is Rs121918394