nhaliday + dementia   15

The Genetics of Alzheimer Disease
Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%–50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes.

Role of Genes and Environments for Explaining Alzheimer Disease: http://jamanetwork.com/journals/jamapsychiatry/fullarticle/209307
study  biodet  twin-study  sib-study  variance-components  candidate-gene  GWAS  medicine  neuro  neuro-nitgrit  dementia  disease  🌞  aging  multi  org:nat  genetics  genomics  immune  health 
september 2017 by nhaliday
Alzheimers | West Hunter
Some disease syndromes almost have to be caused by pathogens – for example, any with a fitness impact (prevalence x fitness reduction) > 2% or so, too big to be caused by mutational pressure. I don’t think that this is the case for AD: it hits so late in life that the fitness impact is minimal. However, that hardly means that it can’t be caused by a pathogen or pathogens – a big fraction of all disease syndromes are, including many that strike in old age. That possibility is always worth checking out, not least because infectious diseases are generally easier to prevent and/or treat.

There is new work that strongly suggests that pathogens are the root cause. It appears that the amyloid is an antimicrobial peptide. amyloid-beta binds to invading microbes and then surrounds and entraps them. ‘When researchers injected Salmonella into mice’s hippocampi, a brain area damaged in Alzheimer’s, A-beta quickly sprang into action. It swarmed the bugs and formed aggregates called fibrils and plaques. “Overnight you see the plaques throughout the hippocampus where the bugs were, and then in each single plaque is a single bacterium,” Tanzi says. ‘

obesity and pathogens: https://westhunt.wordpress.com/2016/05/29/alzheimers/#comment-79757
not sure about this guy, but interesting: https://westhunt.wordpress.com/2016/05/29/alzheimers/#comment-79748

All too often we see large, long-lasting research efforts that never produce, never achieve their goal.

For example, the amyloid hypothesis [accumulation of amyloid-beta oligomers is the cause of Alzheimers] has been dominant for more than 20 years, and has driven development of something like 15 drugs. None of them have worked. At the same time the well-known increased risk from APOe4 has been almost entirely ignored, even though it ought to be a clue to the cause.

In general, when a research effort has been spinning its wheels for a generation or more, shouldn’t we try something different? We could at least try putting a fraction of those research dollars into alternative approaches that have not yet failed repeatedly.

Mostly this applies to research efforts that at least wish they were science. ‘educational research’ is in a special class, and I hardly know what to recommend. Most of the remedial actions that occur to me violate one or more of the Geneva conventions.

APOe4 related to lymphatic system: https://en.wikipedia.org/wiki/Apolipoprotein_E

Look,if I could find out the sort of places that I usually misplace my keys – if I did, which I don’t – I could find the keys more easily the next time I lose them. If you find out that practitioners of a given field are not very competent, it marks that field as a likely place to look for relatively easy discovery. Thus medicine is a promising field, because on the whole doctors are not terribly good investigators. For example, none of the drugs developed for Alzheimers have worked at all, which suggests that our ideas on the causation of Alzheimers are likely wrong. Which suggests that it may (repeat may) be possible to make good progress on Alzheimers, either by an entirely empirical approach, which is way underrated nowadays, or by dumping the current explanation, finding a better one, and applying it.

You could start by looking at basic notions of field X and asking yourself: How do we really know that? Is there serious statistical evidence? Does that notion even accord with basic theory? This sort of checking is entirely possible. In most of the social sciences, we don’t, there isn’t, and it doesn’t.

Hygiene and the world distribution of Alzheimer’s disease: Epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden: https://academic.oup.com/emph/article/2013/1/173/1861845/Hygiene-and-the-world-distribution-of-Alzheimer-s

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease: http://stm.sciencemag.org/content/8/340/340ra72

Fungus, the bogeyman: http://www.economist.com/news/science-and-technology/21676754-curious-result-hints-possibility-dementia-caused-fungal
Fungus and dementia
paper: http://www.nature.com/articles/srep15015
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july 2017 by nhaliday
Associations between education and brain structure at age 73 years, adjusted for age 11 IQ
The significant relationship between education and average cortical thickness (β = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (β = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy.
study  iq  education  neuro  aging  variance-components  dementia  longitudinal  biodet  brain-scan  correlation  behavioral-gen 
october 2016 by nhaliday

bundles : embodied

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