Tag Archives: Alzheimer’s

Feed Your Head – Aβ, Tau & APOE

Aβ plaques & Tau tangles

Fig 1: Pathology of AD showing plaques and tangles.

Some would say a soul is the collective memories and personality traits of an individual. So, what is left if those memories and traits are erased? You and I might be far from old and senile (well I’m not old). But you know someone near & dear to you, who will have to deal with this existential crisis in their golden years. Alzheimer’s disease currently has two culprits, Beta amyloid (Aβ) which can form plaques on the brain and Tau protein, whose over expression can cause neurons to tangle up (NFT).

These pathologies appear to be affected by the APOE gene, certain variations of which are now recognized as dead-ringers for Alzheimer’s. The mechanism however is still very much in the process of being understood. More so, when considering the role of Tau.

Fig 2: Constant expression of plaque causing Aβ with varying levels of Tau shows little difference in pathology. Plaques and tangles remain present. Thus deletion or over expression of Tau is not enough to prevent AD pathology.

Although the signs of Alzheimer’s on a cellular level remained steady while playing with the knobs of Tau expression, the authors did find a difference is the cell & organism survivability. Hypothesizing that Tau helps the neuron deal with excitotoxicity, the damage to nerve cells through stimulation.

Don’t lose hope, although it’s difficult to get a full picture, we may have enough glimpses to make a clinical difference. Eventhough, we don’t quite understand the role between APOE, lipoproteins and Alzheimer’s pathology, on a higher symbolic level APOE is a great predictor of who is at risk for AD and sometimes even when. Best move for now is probably just to get your parents genotyped and planning active mental lifestyles for them, there should be a fix by the time I’m grey.

Citations: Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model by Roberson, et al.

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Filed under Genomics, Neuroimaging, Neurophysiology

Biotech for Hackers: Computational Genomics 1 of 2

A low hurdle to entry along with the ability to iterate rapidly is key to taking on problems & creating solutions. What do these solutions look like in genomics and why can hackers lead the way? Fig 1 shows something very similar to social interaction maps one comes across at places like Facebook.

Fig 1: Interaction map of genes implicated in Alzheimer's. Genes were grouped by those that have similar functions (squares) and those with different functions (circles). Modules with a red border have high confidence interactions. While the weight of the connecting green lines corresponds to the number of interactions between two sets.

The map above is of individual gene relationships where an algorithm began with 12 seed genes that previous experiments have shown to play a role in Alzheimer’s disease. These seeds were compared with 185 new candidate genes from regions deemed susceptible to carrying Alzheimer’s genes. From here, both experimental and computational data was combined to generate Fig 1, which the authors dubbed AD-PIN (Alzheimer’s Disease Protein Interaction Network).

Fig 2: Interactions discovered by the Hig-Confidence (HC) set generated by this study in context to known relationships in the Human Interactome (created in past studies).

What we learn by simply tracking genes already known to play a role in Alzheimer’s is the discovery of new regions of genetic code that are  also participating in the expression of related functions, in this case those being affected by the disease, such as memory. In Fig 2 we see that between seeds this algorithm produced 7 high confidence interaction results, of which 3 were  in common with previous studies. In addition to almost 200 new interactions, which can each lead to new therapies, blockbuster drugs and better understanding of the disease itself.

Many software developers have extensive experience and interest in dealing with large data sets, finding correlations  and creating meaningful solutions. However, much of our generation has had little exposure to these problems. Often resulting in the bandwagon effect, as one recent article put it “the latest fucking location fucking based fucking mobile fucking app.” Progress has often been linked to literacy, from books to programming, being able to read and write in life-code just might be the next stage.

Original published study: Interactome mapping suggests new mechanistic details underlying Alzheimer’s disease by Soler-Lopez et al.

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