From: "jeffrey E." <[email protected]>

From: "jeffrey E." <[email protected]> To: Joi Ito <, Subject: Re: Alzheimer's Date: Thu, 10 Aug 2017 14:43:28 +0000 Leave out brain map Paul Allen's area On Thu, Aug 10, 2017 at 10:34 AM Joi Ito > wrote: Sent from my iPhone Begin forwarded message: From: Ed Boyden Date: August 6, 2017 at 08:13:39 MDT To: Joi Ito Subject: Re: Alzheimer's Reply-To: Papers published so far that are relevant (we'll write up more this Fall): I. Expansion mapping of brains: Science, 2015 - initial discovery: http://synthneuro.org/publications/publicationdetail/229/25 Nature Biotechnology, 2017 - optimization for human specimens: http://synthneuro.org/publications/publicationdetail/270/25 2. 40Hz stim of Alzheimer's: Nature, 2016 - initial discovery: http://synthneuro.org/publications/publicationdetail/260/25 Cell, 2017 - how to noninvasively drive essentially any brain region: http://synthneuro.org/publications/publicationdetail/265/25 Best, Ed On Sun, Aug 6, 2017 at 9:55 AM, Joi Ito > wrote: Can you send me any papers that are published that I could share with Bill? Sent from my iPhone On Aug 6, 2017, at 09:24, Joi Ito .1 I> wrote: EFTA01038996 Very cool. Thanks. Sent from my iPhone On Aug 6, 2017, at 09:11, Ed Boyden Replies below: > wrote: On Sun, Aug 6, 2017 at 9:09 AM, Joichi Ito < > wrote: So to the argument that the plaque is just a byproduct and not the cause of Alzheimer's - we say that we're doing mapping to try to find the cause... Yes, we'll map not just plaque, but also tau, changes in gene expression -- everything we an! but does removing the plaque or some other effect of the 40Hz stimulation show signs that it "helps" Alzheimer's? 40 Hz seems to cause *many* changes, all at once -- not just cleanup of plaque. We see, -- improvements in tau phosphorylation; -- improvements in behavior (unpublished, and not to be disseminated beyond trusted folks); -- improvements in the microglial cells that keep the brain healthy; and other studies are in the works. This is one reason I am excited about 40Hz: it seems to hit somewhere *upstream* of the amyloid, and to help with multiple, independent, downstream effects. Best, Ed EFTA01038997 - Joi On Aug 6, 2017, at 8:52 AM, Ed Boyden < > wrote: Thoughts inline: On Sun, Aug 6, 2017 at 7:19 AM, Joichi Ito < > wrote: Hi Ed, I'm going to be spending a few days with Bill Gates next week and I heard a rumor that he's becoming interested in Alzheimer's research. Very cool! What are you doing these days. Two things: -- Nobody really knows what the earliest changes are, in Alzheimer's. If we could map out the earliest changes, maybe we could halt Alzheimer's fully. This is important because stopping Alzheimer's after the damage has occurred means some functions is already lost. We plan to use expansion microscopy to map out where the earliest changes are, in Alzheimer's, building from our recent adaptation of ExM to work in human tissues, httplAvww.nature.corn/nbt/joumal/vaopincurrent/full/nbt.3892.html? WT.feed_name—subjects_medical-research&foxtrotcallback=true -- We are continuing to work with the labs of Li-Huei Tsai and Tod Machover to define the molecular changes that occur during 40 Hz sensory stimulation (Tsai), to optimize the protocols (Tsai, Boyden, EFTA01038998 Machover), and to design art and media optimal for cleaning up Alzheimer's (Machover). In this way we hope to find a way to halt the progression of Alzheimer's. How is that spinout going? Going well -- we just started human trials! What is your hypothesis and how confident are you? The hypothesis is that 40 Hz sensory stimulation will cause the immune system of the brain to become active, and then to clean up the amyloid plaques and tau changes in Alzheimer's. We are pretty confident: three (!) mouse models of Alzheimer's all showed improvement. The only worry I have is that we will not be able to hit every part of the brain through sensory input -- in which case our backup plan is to use TI stimulation. Is there something easily readable about the work? Alzheimer's 40Hz: https://www.bostonglobe.com/business/20 16/1 2/07/led-technology-from-mit-used-startup-working- alzheimer-treatment/Kbdjp9W v foPL fC 1 bNhvGOI/story.html TI stimulation: https://www.nytimes.com/201 7/06/0 1 /healthinew-eleetrical-brain-stimulation-technique-shows- promise-in-mice.html Best, Ed EFTA01038999 Thanks! - Joi Ed Boyden, Ph. D. Leader, Synthetic Neurobiology Group Associate Professor, MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences Co-Director, MIT Center for Neurobiological Engineering Massachusetts Institute of Technology Building EIS: El 5-421, 20 Ames St., Cambridge, MA 02139 (mailing address) Building 46: 46-2171C, 43 Vassar Street, Cambridge, MA 02139 email - phone - cell - fax - Google Hangout - skype - web - http://syntheticneurobiologyakrg twitter - EFTA01039000 Ed Boyden, Ph. D. Leader, Synthetic Neurobiology Group Associate Professor, MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences Co-Director, MIT Center for Neurobiological Engineering Massachusetts Institute of Technology Building E15: E 15-421, 20 Ames St., Cambridge, MA 02139 (mailing address) Building 46: 46-2171C, 43 Vassar Street, Cambridge, MA 02139 email - phone - cell - fax - Google Hangout - skype - web - http://syntheticneurobiology.org twitter - Ed Boyden, Ph. D. Leader, Synthetic Neurobiology Group Associate Professor, MIT Media Lab and McGovern Institute, Departments of Biological Engineering and Brain and Cognitive Sciences Co-Director, MIT Center for Neurobiological Engineering Massachusetts Institute of Technology Building EIS: E I 5-421, 20 Ames St., Cambridge, MA 02139 (mailing address) Building 46: 46-2171C 43 Vassar Street, Cambridge, MA 02139 email - phone- cell - fax - Google Han out - skype - web - http://syntheticneurobiology.org twitter - please note The information contained in this communication is confidential, may be attorney-client privileged, may EFTA01039001 constitute inside information, and is intended only for the use of the addressee. It is the property of JEE Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. 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