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posted by martyb on Friday August 19 2016, @09:52AM   Printer-friendly
from the finally-some-good-news dept.

Submitted via IRC for cmn32480 with a story that appeared in ScienceAlert:

Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques - structures that are responsible for memory loss and a decline in cognitive function in Alzheimer's patients.

If a person has Alzheimer's disease, it's usually the result of a build-up of two types of lesions - amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.

Neurofibrillary tangles are found inside the neurons of the brain, and they're caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.

[...] Publishing in Science Translational Medicine , the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain's microglial cells to activate. Microglila cells are basically waste-removal cells, so they're able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer's.

The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks - a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.

[...] The team says they're planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017.

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  • (Score: 5, Interesting) by Anonymous Coward on Friday August 19 2016, @02:16PM

    by Anonymous Coward on Friday August 19 2016, @02:16PM (#390077)

    There are more issues than that:

    neurotoxic amyloid plaques - structures that are responsible for memory loss and a decline in cognitive function in Alzheimer's patient

    This is hardly established. All we know is people with memory problems are likely to have more stuff in their brain that stains for this. Also, the neurotoxicity depends on dose and context so it isn't clear the plaques can't be benign or even protective under conditions in the brain. Sorry, I'm too lazy for references right now, but may add some later in the day. Instead anyone interested can search around on pubmed [] for this stuff.

    Some comments on the paper:

    1) Apparently they were not blinded while analyzing the data:

    The treatment condition was kept blinded until the analysis

    This is dangerous because it introduces all sorts of opportunities to look at different outcomes and cherry pick etc. For example when choosing which brain sections to look at, etc. Obviously you need to be unblinded when making the final group comparisons, but if that is what they did I don't see why they would mention "until the analysis".

    2) They collected histological/molecular data for the same mice for which they had behavioral data. A major part of their narrative is that the plaques they measured are related to memory deficits. However, THEY DO NOT PLOT ONE AGAINST THE OTHER. This is a really idiotic practice that is standard in neuroscience research, and yes I checked the supplementary materials.

    3) Basic statistical misunderstandings:

    spontaneous alternation (calculated by the number of complete alternation sequences divided by the number of alternation opportunities) in APP23 mice treated with SUS, but not in sham-treated animals,was restored to wildtype levels [P [less than] 0.05, one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparison] (Fig. 1E). Total entries into the Y-maze arms did not differ between groups (Fig. 1F).

    First, they twice commit the error of "accepting the null hypothesis". Second, no hypothesis about "restoration" was tested. They are comparing different groups of mice at a single timepoint.

    4) More confusion about what hypothesis was actually being tested here:

    Our results revealed that the degree of Ab reduction achieved by SUS treatment was

    They did not measure any "reduction", they compared different groups of mice. If they want to measure "reduction" or "restoration" they would need to figure out a way to measure A-beta multiple times in living mice. Just because this may be hard/impossible doesn't mean they get to leap to claims of "reduction".

    5) These tests of memory may not correspond to what is seen in Alzheimer's, or even be measuring memory. The first one is the Y-maze [] :

    The Y-maze was made of clear Plexiglas and had three identical arms (40 x 9 x 16 cm) 120° apart. The center platform was a triangle with 9 cm side-length. The room was illuminated by 70 lux. Mice were habituated to the testing room and the apparatus 24 h prior to testing by being in the maze for 5 min. On the day of testing mice were placed in one of the arms and allowed to explore the maze for 8 min. Arm entry was defined as having all four limbs inside one of the arms. Mice were videotaped and the videos were analyzed blind. The maze was cleaned with 70% ethanol between animals. The sequence of arm entries was used to obtain a measure of alternation, reflecting spatial working memory. The percentage alternation was calculated by the number of complete alternation sequences (i.e., ABC, BCA, CAB) divided by the number of alternation opportunities (total arm entries minus two).

    They saw the normal/treated mice averaged 60% alternations and the untreated averaged 50%. So this test assumes if a mouse goes in arm A of the maze, then arm B, then goes back to arm A, it must be because it didn't remember what it did a bit earlier. For some reason it is supposed to go to arm C before going again to arm A. There are tons of other explanations for this behavior (maybe the untreated mice were more stressed by bright light, so they tended to avoid the side near the light, maybe their sense of smell was a little worse so they had to go further into each arm (rather than just peeking in) to check for food than the normal mice, maybe they left behind less of a scent).

    I've spent too much time already but maybe this will give someone an idea of what to look for in these papers.

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