# Rapamycin as a preventive intervention for Alzheimer’s disease in APOE4 carriers: targeting brain metabolic and vascular restoration **URL:** \ **Category:** General\ **Created:** [February 2, 2025, 7:41pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519 "2025-02-02T19:41:05Z")\ **Posts on this page:** 20\ **Page:** 1
**Author:** ![RapAdmin](https://www.rapamycin.news/user_avatar/www.rapamycin.news/rapadmin/32/377_2.png) [@RapAdmin](https://www.rapamycin.news/u/RapAdmin)\ **Post date:** [February 2, 2025, 7:41pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/1 "2025-02-02T19:41:05Z")
Neural Regeneration Research ():10.4103/NRR.NRR-D-24-01006, January 29, 2025. | DOI: 10.4103/NRR.NRR-D-24-01006 ![Screen Shot 2025-02-02 at 12.42.07 PM](https://www.rapamycin.news/uploads/default/original/3X/4/a/4a729ea5c3deff276edbeff8bf21618a2d4cdec7.jpeg) > The mTOR pathway is central to maintaining cellular growth, autophagy, and metabolic balance in neurons—processes vital for brain health. In AD, dysregulated mTOR signaling is linked to impaired autophagy and the accumulation of toxic proteins, including Aβ plaques and hyperphosphorylated Tau, which drive neurodegeneration. Additionally, excessive mTOR activation is associated with heightened oxidative stress, mitochondrial dysfunction, and neuroinflammation, all of which exacerbate cognitive decline in AD ([Davoody et al., 2024](https://pubmed.ncbi.nlm.nih.gov/37721413/)). > > Beyond its role as an mTOR inhibitor, rapamycin exerts diverse effects on immune modulation and cellular homeostasis through both mTOR-dependent and independent pathways. It modulates immune responses by influencing T-cell activation and differentiation, promoting immune tolerance through enhanced regulatory mechanisms. Furthermore, rapamycin induces autophagy, a critical cellular process for degrading and recycling damaged proteins and organelles. By activating autophagy, rapamycin may reduce Tau pathology and Aβ accumulation—key drivers of AD progression. This autophagic activation underpins rapamycin’s neuroprotective properties, offering the potential for alleviating AD pathology by clearing neurotoxic aggregates (Davoody et al., 2024). See PDF at bottom of this post: [https://journals.lww.com/nrronline/citation/9900/rapamycin\_as\_a\_preventive\_intervention\_for.690.aspx?fbclid=IwY2xjawIMp8lleHRuA2FlbQIxMAABHRM9SYUaJ\_LsuANf3yyTBpooVyF6NFdC8JiMnlpCwrFxv6r9UGqjejCGoQ\_aem\_XIjRaG4-xSeBwYZ3c9290A](https://journals.lww.com/nrronline/citation/9900/rapamycin_as_a_preventive_intervention_for.690.aspx?fbclid=IwY2xjawIMp8lleHRuA2FlbQIxMAABHRM9SYUaJ_LsuANf3yyTBpooVyF6NFdC8JiMnlpCwrFxv6r9UGqjejCGoQ_aem_XIjRaG4-xSeBwYZ3c9290A) **Related Reading:** - [Rapamycin restores brain vasculature, metabolism, and blood-brain barrier in an inflammaging model](https://www.rapamycin.news/t/rapamycin-restores-brain-vasculature-metabolism-and-blood-brain-barrier-in-an-inflammaging-model/1219) - [Rapamycin and Dementia (not necessarily AD)](https://www.rapamycin.news/t/rapamycin-and-dementia-not-necessarily-ad/8488) - [Rapamycin as a potential treatment for Alzheimer’s disease](https://www.rapamycin.news/t/rapamycin-as-a-potential-treatment-for-alzheimer-s-disease/6989) - [Evaluating the affect of Rapamycin in Alzheimer's disease (ERAP phase IIa clinical study protocol)](https://www.rapamycin.news/t/evaluating-the-affect-of-rapamycin-in-alzheimers-disease-erap-phase-iia-clinical-study-protocol/13852) - [Rapamycin and Alzheimer Disease: a Hypothesis for the Effective use of Rapamycin](https://www.rapamycin.news/t/rapamycin-and-alzheimer-disease-a-hypothesis-for-the-effective-use-of-rapamycin/5448/1) - [A drug cocktail of rapamycin, acarbose, and phenylbutyrate enhances resilience to features of early-stage Alzheimer's disease in aging mice](https://www.rapamycin.news/t/a-drug-cocktail-of-rapamycin-acarbose-and-phenylbutyrate-enhances-resilience-to-features-of-early-stage-alzheimers-disease-in-aging-mice/12227) - [Alzheimer's Disease and Rapamycin](https://www.rapamycin.news/t/alzheimers-disease-and-rapamycin/17293) [rapamycin\_as\_a\_preventive\_intervention\_for.690.pdf](https://www.rapamycin.news/uploads/short-url/auM4TwuNnpjYhYZsd8MXcwdjFqi.pdf) (6.0 MB) ---
**Author:** ![complexworld](https://www.rapamycin.news/user_avatar/www.rapamycin.news/complexworld/32/27560_2.png) [@complexworld](https://www.rapamycin.news/u/complexworld)\ **Post date:** [February 7, 2025, 2:51am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/2 "2025-02-07T02:51:25Z")
I improvements like that I almost wish I was an APOE4 mouse (technically E4FAD), instead of an APOE4 human! ![Screenshot_20250206-182128](https://www.rapamycin.news/uploads/default/original/3X/8/4/84e9f883f5d9cd36370d28065d9a2c1aa6dbf006.png) I’m a beginner when it comes to reading scientific publications. I wasn’t able to see the description of the experiments (how many mice, groups, etc) that produced this data. I must have missed something because,I don’t understand what value this publication provides. It writes about things that are well known: e.g. the APOE4 allele increases Alzheimer risk. And then it quotes data from other publications. Where’s the meat? What am I missing? ---
**Author:** ![Skyzercise](https://www.rapamycin.news/user_avatar/www.rapamycin.news/skyzercise/32/9119_2.png) [@Skyzercise](https://www.rapamycin.news/u/Skyzercise)\ **Post date:** [February 8, 2025, 12:11am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/3 "2025-02-08T00:11:34Z")
I’m an APOE4 carrier and that article was great to read. thank you for sharing that! ---
**Author:** ![Agetron](https://www.rapamycin.news/user_avatar/www.rapamycin.news/agetron/32/40772_2.png) [@Agetron](https://www.rapamycin.news/u/Agetron)\ **Post date:** [February 8, 2025, 1:40am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/4 "2025-02-08T01:40:42Z")
Yes… Ai Ling Lin, Ph.D is very thorough… we chatted a lot about rapamycin benefits…and potential side effects before she started her clinical trial. Small group… but the benefits you’d expect from rapamycin. ---
**Author:** ![Jonas](https://www.rapamycin.news/user_avatar/www.rapamycin.news/jonas/32/11713_2.png) [@Jonas](https://www.rapamycin.news/u/Jonas)\ **Post date:** [February 11, 2025, 8:45pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/5 "2025-02-11T20:45:12Z")
Published recently. Small study, positive result. Dose was 1mg per day. Alzhermer’s trial called by Matt Kaeberlein ![Screenshot 2025-02-11 at 10.44.48 AM](https://www.rapamycin.news/uploads/default/original/3X/6/1/61160b3c3432cf738b9817bdb9fb8eee551861f8.jpeg) Source paper: [Rapamycin as a preventive intervention for Alzheimer’s disease in APOE4 carriers: targeting brain metabolic and vascular restoration](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519) From [Optispan Podcasts](https://www.youtube.com/playlist?list=PLYkGEUWjgK_cDjiNWSUq5pboQ-NTt_EQr) [![](https://img.youtube.com/vi/b76K5PU3rfE/maxresdefault.jpg "The Effects of Rapamycin on APOE4 Carriers & Brain Function") ](https://www.youtube.com/watch?v=b76K5PU3rfE) ---
**Author:** ![dicarlo2](https://www.rapamycin.news/user_avatar/www.rapamycin.news/dicarlo2/32/29246_2.png) [@dicarlo2](https://www.rapamycin.news/u/dicarlo2)\ **Post date:** [February 11, 2025, 9:21pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/6 "2025-02-11T21:21:19Z")
Very interesting. The 1mg/day dose further adds to my confusion around intermittent dosing vs low daily doses. ---
**Author:** ![medaura](https://www.rapamycin.news/letter_avatar_proxy/v4/letter/m/c0e974/32.png) [@medaura](https://www.rapamycin.news/u/medaura)\ **Post date:** [February 11, 2025, 9:41pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/7 "2025-02-11T21:41:54Z")
Yeah when I’m back on Rapa (around July / August at this rate) I’ll do 1 mg / day for a time, maybe a few months, and see what happens. I’m almost sure it won’t be optimal to keep up that dose forever and periodic breaks will be needed, and maybe a switch to ultra high dose low frequency like @John_Hemming’s. But what I am curious about is HOW sirolimus was able to exert this effect at this dose, seeing as it doesn’t cross the BBB unless at a much higher and prolonged concentration. Though the evidence for the latter statement always seemed too spotty and hypothetical. There’s also the increased BBB permeability of apoE4 carriers like myself so that probably works in favor of drug penetration. ---
**Author:** ![Agetron](https://www.rapamycin.news/user_avatar/www.rapamycin.news/agetron/32/40772_2.png) [@Agetron](https://www.rapamycin.news/u/Agetron)\ **Post date:** [February 11, 2025, 9:56pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/8 "2025-02-11T21:56:45Z")
Hahaha, Matt says people in the know call rapamycin - Vitamin R ! Great. ---
**Author:** ![A\_User](https://www.rapamycin.news/user_avatar/www.rapamycin.news/a_user/32/40991_2.png) [@A\_User](https://www.rapamycin.news/u/A_User)\ **Post date:** [February 11, 2025, 10:07pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/9 "2025-02-11T22:07:10Z")
> [@medaura](#): > > seeing as it doesn’t cross the BBB unless at a much higher and prolonged concentration. It probably does cross the BBB at a typical 6 mg dose: > [@Parkinson's disease](https://www.rapamycin.news/t/parkinsons-disease/6400/488): > > I don’t know if you’ve seen this paper (there’s so many papers & discussions). There are a few threads on ketamine & rapamycin and videos from the lead author of the experiment which showed rapa prolonging the anti-depressant effect (they tried it because they believed it would block it). From the paper it seems that it does cross the BBB: Using a randomized placebo-controlled cross-over design, rapamycin was administered as a single 6 mg dose prior to ketamine infusion. In several species, preclinical studies have shown that rapamycin crosses the blood brain barrier, as measured by rapamycin levels in the cerebrospinal fluid and brain tissues, or by the inhibition of brain mTORC1 signaling [[23](https://pmc.ncbi.nlm.nih.gov/articles/PMC7162891/#CR23)–[26](https://pmc.ncbi.nlm.nih.gov/articles/PMC7162891/#CR26)]. Moreover, within 2 h following peripheral rapamycin administration, one study reported decreased phosphorylation of S6 ribosomal protein in brain tissues—a pharmacodynamic readout of mTORC1 inhibition [[15](https://pmc.ncbi.nlm.nih.gov/articles/PMC7162891/#CR15)]. Furthermore, the immunosuppressive effect of rapamycin is an mTORC1-dependent p… ---
**Author:** ![DrFraser](https://www.rapamycin.news/user_avatar/www.rapamycin.news/drfraser/32/21601_2.png) [@DrFraser](https://www.rapamycin.news/u/DrFraser)\ **Post date:** [February 12, 2025, 1:41am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/10 "2025-02-12T01:41:59Z")
In regard to the dosing, safety is a factor - but you’ll likely have some immunosuppression and adverse effects if you take 1 mg/day. We’d need to see levels. I’d say most people can get away with this for 1 month, but on a safety basis, I’d be very reluctant to dose this way longer term. ---
**Author:** ![medaura](https://www.rapamycin.news/letter_avatar_proxy/v4/letter/m/c0e974/32.png) [@medaura](https://www.rapamycin.news/u/medaura)\ **Post date:** [February 12, 2025, 2:02am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/11 "2025-02-12T02:02:12Z")
But this was 1 mg/day not 6. ---
**Author:** ![adssx](https://www.rapamycin.news/user_avatar/www.rapamycin.news/adssx/32/14464_2.png) [@adssx](https://www.rapamycin.news/u/adssx)\ **Post date:** [February 12, 2025, 8:50am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/12 "2025-02-12T08:50:04Z")
I merged the two threads, thinking they were about the same paper, but they’re not. The first paper is [Rapamycin as a preventive intervention for Alzheimer’s disease in APOE4 carriers: targeting brain metabolic and vascular restoration](https://journals.lww.com/nrronline/citation/9900/rapamycin_as_a_preventive_intervention_for.690.aspx) 2025 This paper by Ai-Ling Lin does not say anything new. It only comments on a previous paper, also by Ai-Ling Lin (the figures come from there if I’m correct): [mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner](https://journals.sagepub.com/doi/abs/10.1177/0271678X241261942) 2024 Matt Kaeberlein discusses another paper in his podcast: [Short-term Sirolimus Treatment Restores Hippocampus and Caudate Volumes and Global Cerebral Blood Flow in Asymptomatic APOE4 Carriers Compared with Non-carriers](https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.094114). Also by Ai-Ling Lin and also from Jan 2025 (hence the confusion): > Low dose Sirolimus (1 mg/day) was given for 4 weeks to three middle-aged, cognitively normal APOE4 carriers (F:M = 2:1) and two female APOE3 individuals (45-65 yrs; MOCA \> 27). > APOE4 carriers had significantly increased Caudate and Hippocampal volumes (Fig. 1A) and gCBF (Fig. 1B) after 4 weeks of Sirolimus treatment. > No side effects were observed, and no changes in blood glucose and HbAc1 levels were found in all the participants. ![image](https://www.rapamycin.news/uploads/default/original/3X/f/9/f9ade440b84a24978e3d19c27893d729416aa630.jpeg) ![image](https://www.rapamycin.news/uploads/default/original/3X/b/d/bd1c0792368ba346446f25350897c0f578e49d5c.png) Tiny study (n=5), not randomized, not placebo controlled. It would have been great to measure after one month without rapamycin to see whether the biomarkers return to baseline or stay high. If they stay constant, then one could just do 4 weeks of 1 mg/day once a year to protect their brain. Or a single yearly large dose (@John_Hemming’s strategy?). Anyway, I wasn’t convinced by rapa’s neuroprotective potential but there’s a growing body of evidence… Also: is there a risk with low-dose rapa (1 mg/day vs 5 or 6 mg/week)? See: > [@Top 5 - Which Currently Available Longevity Interventions Do You Think Are the Best](https://www.rapamycin.news/t/top-5-which-currently-available-longevity-interventions-do-you-think-are-the-best/15891/201): > > Interesting tidbits on rapamycin low dosing. I post this here because it is a more active thread. David Glass is VP at $REGN, he is a bull on rapamycin. ---
**Author:** ![John\_Hemming](https://www.rapamycin.news/user_avatar/www.rapamycin.news/john_hemming/32/6542_2.png) [@John\_Hemming](https://www.rapamycin.news/u/John_Hemming)\ **Post date:** [February 12, 2025, 8:57am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/13 "2025-02-12T08:57:45Z")
> [@adssx](#): > > Or a single yearly large dose (@John_Hemming’s strategy?). I was working on every 6 weeks, but have stopped for a bit because I wish to understand what is happening to my leucocytes. ---
**Author:** ![adssx](https://www.rapamycin.news/user_avatar/www.rapamycin.news/adssx/32/14464_2.png) [@adssx](https://www.rapamycin.news/u/adssx)\ **Post date:** [February 12, 2025, 9:06am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/14 "2025-02-12T09:06:36Z")
> [@adssx](#): > > Anyway, I wasn’t convinced by rapa’s neuroprotective potential but there’s a growing body of evidence… Caveat: the CARPE\_DIEM phase 1 trial of rapa 1 mg/day in AD found worse cognition scores after 8 weeks and 0 rapa in the CSF: [ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT04200911?tab=results) They’re still following up with phase 2 ([NCT04629495](https://clinicaltrials.gov/study/NCT04629495)), n=40, results in 2026. The ERAP trial in AD ([NCT06022068](https://clinicaltrials.gov/study/NCT06022068)) is supposed to have just completed. “7 mg taken once per week during 26 weeks.” So we should expect results soon? I’ve just emailed the researcher. In their protocol, they wrote: > Notably, the data on side effects is based on the use of rapamycin following organ transplantation, where the drug is commonly used together with other immunosuppressants. In the ERAP trial, we plan to deviate from the standard dosing of rapamycin in two ways. Typically, when used as an immunosuppressant, rapamycin is administered orally at a daily dose of 2 mg or above [43]. We will instead administer an overall lower dose but in an intermittent fashion; a weekly oral dose of 7 mg. This change is aimed at reducing the risk of adverse events. The rationale behind this is that positive effects of rapamycin are hypothesized to be caused by inhibition of the mTOR1 complex, while many of the side effects are hypothesized to be due to inhibition of the mTOR2 complex. While mTOR1 is sensitive to acute dosing treatment, mTOR2 requires sustained exposure of the drug to be effectively inhibited [45]. > The extent to which rapamycin crosses the blood-brain barrier (BBB) in humans has not been thoroughly investigated. Rapamycin is a large molecule (molecular weight 914.2) and a substrate, albeit with low affinity, for the efflux pump P-glycoprotein [[46](https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03596-1#ref-CR46)]. Compounds with these properties are often considered unlikely to pass from intestine to blood and bind to an intracellular target [[47](https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03596-1#ref-CR47)]. It is however known, from long clinical use, that oral treatment with rapamycin in humans leads to intracellular mTOR inhibition. The molecule’s ability to pass through cell membranes , likely facilitated by its high lipophilicity (logP estimated to be 4.3), **supports its passage across the BBB despite its size .** > After oral administration, **detectable levels of rapamycin have been found in the brains of rodents** [49, 50], and a large number of studies show clear effects in the central nervous system of animals [7]. Support for cerebral target engagement (i.e. mTOR inhibition) in humans comes from the use of rapamycin as a first-line treatment for the cerebral manifestations of TSC [51]. TSC is a genetic disorder that activates the mTOR pathway, leading to the growth of benign tumors in various organs, including the brain. Inhibition of mTOR with rapamycin analogues is the only approved pharmacological treatment of the disease, and the only feasible mechanism of action is mTOR inhibition in cells behind the BBB. They also give three possible mechanisms of action of rapa: autophagy (mTOR inhibition), vasculoprotection (“Rapamycin has been shown to improve cerebral perfusion and BBB integrity in rodent models of AD, supporting the notion of the mTOR pathway as a potential target for brain vasculoprotection in AD”) and immunomodulation. So hopefully, we’ll get an answer very soon (this year) about the effectiveness of 7 mg/week in AD. And next year about 1 mg/day. ---
**Author:** ![John\_Hemming](https://www.rapamycin.news/user_avatar/www.rapamycin.news/john_hemming/32/6542_2.png) [@John\_Hemming](https://www.rapamycin.news/u/John_Hemming)\ **Post date:** [February 12, 2025, 9:53am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/15 "2025-02-12T09:53:02Z")
Rapamycin causes a reduction in WBC via inhibition of mTORC1. This is arguably a side effect from the main mechanism. The reduction in WBC results in more infections which is one of the things that people don’t like. Similarly Rapamycin causes hepatic insulin resistance via inhibition of mTORC1. It will also reduce the production of stem cells. I have not myself looked that much at mTORC2, but I think people should be aware that a lot of the negative effects of rapamycin come directly from its main mechanism of action and all that can be done is to adjust dosing strategies to obtain the greatest benefit for the least sensible harm. ---
**Author:** ![adssx](https://www.rapamycin.news/user_avatar/www.rapamycin.news/adssx/32/14464_2.png) [@adssx](https://www.rapamycin.news/u/adssx)\ **Post date:** [February 12, 2025, 10:26am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/16 "2025-02-12T10:26:50Z")
> [@John\_Hemming](#): > > It will also reduce the production of stem cells. Urolithin A might be better than rapa regarding this: [Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU - #297 by adssx](https://www.rapamycin.news/t/urolithin-a-ua-one-of-4-promising-agents-2024-by-brian-kennedy-of-nsu/11219/297) ---
**Author:** ![John\_Hemming](https://www.rapamycin.news/user_avatar/www.rapamycin.news/john_hemming/32/6542_2.png) [@John\_Hemming](https://www.rapamycin.news/u/John_Hemming)\ **Post date:** [February 12, 2025, 11:58am UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/17 "2025-02-12T11:58:41Z")
It reduces stem cells as a result of inhibiting mTOR. ---
**Author:** ![L\_H](https://www.rapamycin.news/user_avatar/www.rapamycin.news/l_h/32/7125_2.png) [@L\_H](https://www.rapamycin.news/u/L_H)\ **Post date:** [February 12, 2025, 2:30pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/18 "2025-02-12T14:30:27Z")
The study used 1mg/d but only for 4 weeks! ---
**Author:** ![adssx](https://www.rapamycin.news/user_avatar/www.rapamycin.news/adssx/32/14464_2.png) [@adssx](https://www.rapamycin.news/u/adssx)\ **Post date:** [February 12, 2025, 2:45pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/19 "2025-02-12T14:45:52Z")
> [@adssx](#): > > The ERAP trial in AD ([NCT06022068](https://clinicaltrials.gov/study/NCT06022068)) is supposed to have just completed. “7 mg taken once per week during 26 weeks.” So we should expect results soon? I’ve just emailed the researcher. They got back to me: “We are hoping to have **some results ready around May-June** , but it is always difficult to say with any certainty.” ---
**Author:** ![DrFraser](https://www.rapamycin.news/user_avatar/www.rapamycin.news/drfraser/32/21601_2.png) [@DrFraser](https://www.rapamycin.news/u/DrFraser)\ **Post date:** [February 12, 2025, 2:56pm UTC](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519/20 "2025-02-12T14:56:25Z")
As Matt pointed out on the podcast, it is such a pity that we cannot solve this once and for all. Probably need a cohort of one off one month of daily rapamycin, another with weekly dosing targeted to blood levels, and placebo with individuals all ApoE4/E4. The costs would be probably 3 MRIs including cerebral blood flow, Initial, 2 months, 12 months. In this fashion we’d see if cyclic was effective (and doing this for the whole 12 months), or whether a one time month of daily rapamycin has effects and sticking power (I’d propose the group on longer cyclic therapy will have further improvements on their 1 year scan as compared to the their 2 month scan, whereas I’d bet the group that did the 1 month then stopped will have some regression). Then we’d need the placebo to see the natural rate of progression of disease with no treatment. These things are very complicated to arrange, but I’d bet that it wouldn’t be that hard to find 300 people willing to self fund their labs, 3 MRI’s who have ApoE4/E4. I wonder if an organization like the Buck Institute would pursue this? [Next page](https://www.rapamycin.news/t/rapamycin-as-a-preventive-intervention-for-alzheimer-s-disease-in-apoe4-carriers-targeting-brain-metabolic-and-vascular-restoration/18519.md?page=2)