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nt of the neurofibrillary tangle is the tau protein which has been modified by adding phosphate groups to it so it can no longer do its normal job of binding to proteins form long tubular structures in neurons e g microtubules this is what the norwegians measured tau protein with an added phosphate group at amino acid number 217 ptau217 they measured ptau217 in the blood not the brain they did not do pet scans to measure p217 in the brain or neurofibrillary tangles however it was found in a study of 786 patients that blood ptau217 did predict the results of pet scans which do measure tau protein and by inference neurofibrillary tangles jama neurology vol 81 pp 255 263 24 we are thusly separated by a long and delicate chain of inferences from actually visualizing the neuropathologic changes of alzhimer s at autopsy don t forget this i d like to see the jama paper replicated at any rate an elevated ptau217 level in the blood is taken to mean increased neurofibrillary tangles in the brain e g one of the two neuropathological changes of alzheimer s the work uses data from a prospective research study trondelag health study hunt study beginning in 1984 starting with 250 000 people a new wave begins ever 10 years they used blood from 11 486 people over 58 immediately you notice one of the strengths of the study more than 10 times as many people in it than the above jama study making its findings far more solid statistically some 8 949 hunt participants over 70 had cognitive testing impressive and far larger than other studies 10 of 8 949 norwegians over 70 had elevated ptau217 and dementia e g alzheimer s disease by study criteria 2 10 of the 8 949 had mild cognitive impairment and elevated ptau217 in blood called early alzheimer s 3 10 of 8 949 over 70 had elevated ptau217 and no dementia maybe they ll develop it later but it confirms what autopsy work over the last century has shown consistently there are plenty of people with all the neuropathological changes of alzheimer s and no dementia at all i had no idea the percentage was so high and neither did anyone else there is much more in the paper but it s basically a distraction from the main point of this post a positive ptau217 test does not mean you have alzheimer s if you are not demented sadly a negative ptau217 test does not mean you aren t demented 19 of demented patients in the study had normal ptau217 levels this actually makes sense as there are many more causes of dementia than alzheimer s stroke trauma alcoholism severe diabetes liver and kidney failure the list is endless february 14 2026 3 09 pm categories neurology psychiatry uncategorized post a comment tagged alzheimer neuropathological changes amyloid plaque diagnosis of alzheimer s disease hunt study neurofibrillary tangle p217tau positron emission tomography pet scan presenile dementia senile plaque tau protein trondelag health study the bias of the unbiased take ii i ve published nearly 1 300 posts over the years and each day wordpress tells me how many people looked at my blog chemiotics ii and which posts they looked at a post from the pre chatgpt era was seen which is relevant to the upheavals of the press today particularly cbs so i m doing something i ve never done republishing an old post while possession is ninetenths of the law may or not be true perception is ninetenths of politics certainly is npr was defunded because the right viewed it as biased and fox news certainly is but what if you re so biased that you don t realize it while writing a paper on bias here s the old post from 22 april 2018 enjoy the bias of the unbiased a hilarious paper from stanford shows the bias of the unbiased proc natl acad sci vol 115 pp e3635 e3644 18 no one wants to be considered biased or to use stereotypes but this paper indicts all of us they use a technique called word embedding to look at a large body of printed material wikipedia google news articles etc etc over the past 100 years to look for word associations e g male trustworthy female submissive and the like in word embedding models each word in a given language is associated with a high dimensional vector not clear to me how the dimensions are chosen and the metric between the words is measured a metric is simply a mathematical device that takes two objects and associates a number with them the distance between cities is a good example the vector for france is close to vectors for austria and italy the difference between london and england obtained by subtracting them is parallel to the difference between to the difference between paris and france this allows embeddings to capture analogy relationships such as london is to england as paris is to france so word embeddings were used as a way to study gender and ethnic stereotypes in the 20th and 21st centuries in the usa not only that but they plotted how the biases changed over time so in your mind the metric between bias bad stereotype worse is clear so just as women s occupations have changed so have the descriptors of women back in the day women if they worked out of the home at all were teachers or nurses a descendent of jonathan edwards a dominant congregational minister of the 1700 s was a grade school teacher in the town of my small rural high school as women moved into the wider workforce the descriptors of them changed the following is a pair of direct quotes from the article more importantly these correlations are very similar over the decades suggesting that the relationship between embedding bias score and reality as measured by occupation participation is consistent over time this consistency makes the interpretation of embedding bias more reliable i e a given bias score corresponds to approximately the same percentage of the workforce in that occupation being women regardless of the embedding decade english translation as women s percentage of workers in a given occupation changed the bias score changed with it so what the authors describe and worse define as bias and stereotyping is actually an accurate perception of reality we re all guilty the authors are following humpty dumpty in alice in wonderland when i use a word humpty dumpty said in rather a scornful tone it means just what i choose it to mean neither more nor less the question is said alice whether you can make words mean so many different things the question is said humpty dumpty which is to be master that s all i find the paper hilarious and an example of the bias of the supposedly unbiased february 12 2026 10 07 pm categories philosophical issues raised social issues be civil post a comment tagged bias bias amazingly described as an accurate description of reality cbs johnathan edwards npr perception is ninetenths of politics possession is ninetenths of the law pre chatgpt era word embeddings another scientific sewer autism and the microbiome to leave no one behind the microbiome is all the organisms mostly bacterial but viral fungal protozoal and god knows what else that live in our gastrointestinal tract a tremendous article in the current issue of neuron vol 114 pp 196 211 26 dissects the literature on the relationship of the microbiome to autism a lot of what follows is a direct lift from the article modified for clarity and verbosity i ve put in my own comments but it is not my work we now have an average of 102 articles each year on the relationship of the microbiome to autism since the first article on the subject appeared in 2011 two population studies have found no increase in rates of autistic symptoms in the population even as rates of diagnoses became higher in younger cohorts 2011 2015 couldn t they have come up with more recent references rates of gi symptoms in children with autism are consistently significantly higher than in typically developing td children e g 33 versus 15 an pediatr engl ed 2023 99 102 110 gi comorbidities are also high in people with intellectual disability or developmental delays more generally including down syndrome for example human observational studies the twelve most cited studies 107 1 219 citations which say there is something to the association are reviewed the make up much of the evidence base of the meta analyses the sample sizes are small 7 to 43 people no hypotheses were given at the start there was failure to account for multiple statistical tests in all and no replication the dangers of conducting exploratory analyses of high dimensional data with small samples are now well known and have contributed to the replication crisis across many disciplines particularly gwas genome wide association studies major league baseball with little statistical training figured this out a century ago joe sixpack with 6 hits in 8 at bats with a batting average of 750 was not a candidate for the best hitter in baseball now 502 at bats are needed they knew statistical flukes were likely with small numbers as you might expect the findings of the 12 studies were inconsistent which microbes in autistic kids differ from normals how they differ from normals which metabolites differ from normal levels of microbial diversity lower the same or higher the only two studies using sibs as controls found no significant differences even for factors with known impact on the microbiome including age body mass index bmi fruit consumption or a range of metabolic conditions require samples of several hundred to detect the largest effects and thousands for the smallest these conclusions align with those of rothschild et al who found robust microbiome associations with various phenotypes e g age bmi diabetes and smoking status in very large samples 34 000 individuals but they report that when sub sampling our large cohort into smaller sized cohorts we found that even cohorts of 1 000 individuals have significantly lower average accuracy of associations between bacteria and phenotypes they conclude that these results may explain the relatively low agreement that exists across studies in the set of bacteria associated with different traits and conditions and they call for employing larger cohort sizes in microbiome studies the inference seems to be that even if specific findings are inconsistent most of the published studies that have examined the question have found some differences in the microbiome of autistic people compared with td controls this is often couched in more general terms with claims of dysbiosis of the gut microbiome in individuals with autism as pointed out by researchers in the field this is a vague term which effectively captures any profile of differences regardless of consistency two studies showing directly contradictory profiles of change could both be classed as evidence of dysbiosis even worse the effect sizes when found are small 3 5 the use of mouse models of autism is criticized are there even autisticlike behaviors in mice the most widely used mouse assays of behavior are 1 marble burying 2 the three chamber social approach and 3 ultrasonic vocalization usv e g high pitched cries we can t hear in marble burying a number of marbles are placed on top of the bedding in the mouse s cage and the mouse s tendency to dig in the bedding leads to them becoming buried this is believed to tap into stereotyped and compulsive behavior and to be related to repetitive behaviors in people with autism the three chamber social approach assay measures the preference of an animal to explore another mouse compared with an inanimate object or a novel mouse compared with a familiar one this is taken to be a proxy for social cognition and behavior in people with autism rodents emit usvs in diverse social situations across their lifespan and these are taken to have a communicative function usvs can be assayed in the lab under various conditions and are claimed to be relevant to the core symptoms of communication deficits in human patients one issue with this particular assay is that both increases and decreases in usvs have been interpreted as autistic like behaviors in addition to these behavioral tests a wide range of other assays may also be performed to assess arousal locomotor activity motor coordination anxiety stereotypy learning and memory and other parameters attempts have been made to put the human fecal microbiome into mice and look for effects but 85 of bacterial genera found in the mouse microbiome not present in man a substantial proportion of the species that comprise the human gut microbiome fail to colonize in the recipient animals and that species that do colonize assemble into communities that differ substantially from those found in the human donors there are three seminal papers prominently cited as providing evidence that intervening on the microbiome in mice can either cause or treat autism related behaviors according to google scholar as of may 19th 2025 these are the most highly cited studies in this field with 3 739 1 245 and 1 107 citations respectively 1 paper there is no good evidence that maternal immune activation has any causal involvement in autism etiology a number of studies have found a small increased risk of autism in the offspring of mothers exposed to infections during pregnancy sometimes only when subdividing cohorts by some covariates such as the semester of pregnancy in which the infection occurred the final paper of this set 3 by sharon and colleagues ostensibly offered the most direct test of the causal involvement of the microbiome in autism the authors claimed that colonization of mice with gut microbiota from human donors with asd but not from td controls is sufficient to promote behaviors in mice consistent with the core behavioral features of asd a tiny sample set 8 asd 5 normals pathetic deeper problems with the statistical analyses were discovered post publication in particular the authors had treated each mouse as an independent observation when they should have been treated as experimental replicates of transplants from specific donors to their credit the authors made their primary data and code available for reanalysis when the data were analyzed with the appropriate statistical model the supposedly significant differences disappeared with the exception of marble burying where the remaining effect is statistically significant but very small the main claims of the paper thus rest on flawed analyses and do not stand up to statistical scrutiny what a waste of taxpayer money my comment two human studies of fecal transplants as therapy were large 40 and 49 autistics but the design was open label not randomized controlled trials however one double blind randomized clinical trial of fecal microbiota transplant fmt in children with autism spectrum disorder asd has been reported randomizing 52 to fmt and 51 to placebo the study failed to find any between arm differences in improved clinical symptoms in children across three separate scales srs 2 t score primary abc scores or vineland 3 composite score in an apparently post hoc analysis of outcomes they did...