FamilyHistory wrote: ↑Sat Jun 08, 2024 5:14 pm
Since Alzheimer's has also causal factors in the gut microbiome, this promising fecal implant for Parkinson's symptomatic improvement,
https://www.thelancet.com/journals/ecli ... 1/fulltext, and the reverse (fecal implant from humans with Alzheimer's causes cognitive decline and biomarkers in rats
https://academic.oup.com/brain/article/ ... ogin=false ), this approach gives me possible hope for fecal implant treatment to improve hippocampal neurogenesis...... These mouse studies in this post also seem promising.
Could somewhat simple one-time fecal transplant prevent decline in those with 1 or 2 copies of Apoe4? Thoughts or new findings???
Welcome to the forum, "FamilyHistory",
Given your username, I am taking a mild leap in assuming you have a family history of Alzheimer's and/or other neurological disorders, and either one or two copies of ApoE4. If so, you and I have both of those things in common, and you have the edge on me in reading one of the Lancet's e-journals on Clinical Medicine to find this intriguing, open-access article from very recent research.
High levels of cognitive reserve (high education, high occupational challenge, intellectual curiosity) have repeatedly been shown to correlate strongly with cognitive resistance to the genetic risks of ApoE 4. You're showing all of that and raising thought-provoking questions !
Because this topic may get a lot of interest, I'm going to use your link to share some of what the study had to say. Sharing studies and discussing their potential impact is a favorite pastime on the forum and one I hope you will continue to join in on!
For those whose family history does not include Parkinson's, here's a brief overview from the article about their reasoning, with emphasis added:
The pathological hallmark of PD, alpha-synuclein aggregates, has been observed in the gastrointestinal system during the prodromal phase of the disease. This aggregated alpha-synuclein can reach the brain via the vagal nerve, which has been shown directly in animal models and indirectly by an apparent reduced risk of developing PD after vagotomy. These findings led to the dual-hit Braak hypothesis which states that alpha-synuclein aggregation is triggered by microbiota at the level of the gut and/or the olfactory nerves. Recently, this hypothesis has been expanded to a body-first or brain-first onset of PD. In the body-first phenotype, pathology is believed to start in the gut and emerging evidence suggests that the gut microbiome may play this pivotal role in PD pathogenesis and progression.
Below is an excerpt of the results in a group of 21 patients who received health donor microbiota vs. 22 people with similar disease stage who received a "placebo" treatment of their own donated microbiota. {Everyone donated their own stool, so both participants and investigators were "blinded" as to who received which treatment, similar to current anti-amyloid drug infusions of a drug or a saline solution.
At the 12-month mark, the primary outcome measure, namely the MDS-UPDRS motor scores in an off-medication state, showed improvement in the healthy donor FMT group with a decrease of 5.8 points (95% CI −11.4 to −0.2) compared to 2.7 points (−8.3 to 2.9) in the placebo group (Table 2; Fig. 2). The change in MDS-UPDRS motor score from baseline to 12 months post-FMT was significantly different between treatment groups (p = 0.0235; Table 2; Fig. 2), with the most important between-group deviation in the 6-to-12-months interval. The placebo FMT group experienced an increase in the number of radiopaque pellets by 6.9 pellets (2.0–11.8) corresponding to an increased colon transit time, whereas the active treatment group had a small decrease of 1.2 pellets (−6.1 to 3.7) (p = 0.0252; Table 3; Fig. 3).
Additionally, the healthy donor FMT group demonstrated worse performance on the Parkinson's Fatigue Scale (p = 0.0418; Table 3). There were no significant differences between the treatment groups in other scores of the MDS-UPDRS (part 1, part 2, part 4, and part 1–4 total score; Table 2), the LEDD, the Non-Motor Symptoms Scale for Parkinson's Disease, the Parkinson's Disease Quality of Life Questionnaire, Wexner Constipation Scale, Geriatric Depression Scale, Parkinson Anxiety Scale, Lille Apathy Rating Scale, Parkinson's Disease Sleep Scale, and Montreal Cognitive Assessment (Table 3).
Most Phase 1-2 trials want to see if a treatment is safe first of all, and if it shows indications of benefit on a meaningful and measurable "primary outcome". Often several other "secondary outcomes" are also studied in hopes of seeing some "signal' of an effect, but recognizing that those areas, especially if they involve behavioral or daily living skills, often change slowly in the normal course of events.
Often the small numbers of people in an early trial don't allow for terms like "statistically significant", which require sometimes hundreds or thousands of people. This study was well-designed to have enough people to find a trend towards a meaningful benefit in a PD motor score--and it looks like it shows that trend, with only about 2% likelihood that the results were due to chance. But other aspects of PD, probably as expected, didn't show a change.
Having had a maternal uncle with Parkinson's with dementia, and a mother and several maternal aunts with Alzheimer's and/or vascular dementia, I think the possible links of ApoE 4 to both are worth studying! It remains to be seen if alpha-synuclein, the signature mis-folded protein of PD and Lewy Body Dementia, is the only mis-folded protein that can reach the brain through the vagus nerve, or if other forms of GI inflammation can be treated in people at genetic risk of AD and reduce or prevent amyloid plaques and tau tangles. I hope this article in a journal with the impact of the Lancet drives some more funding towards this hypothesis!
In case you are looking for broader overviews of the strategies used by many on the forum, the
Primer written by Stavia, a practicing M.D. with ApoE4/4, is a great resource. She has a bibliography at the end of her index of strategies with possible biomarkers to monitor.
The
How-To Guide shows how to quote members (use the
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And if you'd like to share more of the family history and scientific curiosity and acumen that led you here, feel free to post on
Our Stories.
Nancy
