Targeting early tau pathology: probiotic diet enhances cognitive function and reduces inflammation in a preclinical Alzheimer’s model
Bibliographic record
Abstract
Alzheimer’s disease (AD) remains incurable, yet its long prodromal phase offers a crucial window for early intervention. Pretangle tau, a precursor to neurofibrillary tangles, plays a key role in early AD pathogenesis. Intervening in pretangle tau pathology could significantly delay the progression of AD. The gut-brain axis, increasingly recognized as a contributor to AD, represents a promising therapeutic target due to its role in regulating neuroinflammation and neurodegeneration. While probiotics have shown cognitive benefits in amyloid-centered AD models, their effect on pretangle tau pathology remains elusive. This study evaluates the effects of probiotics in a rat model of preclinical AD, specifically targeting hyperphosphorylated pretangle tau in the locus coeruleus. TH-CRE rats ( N = 47; 24 females and 23 males) received either AAV carrying pseudophosphorylated human tau (htauE14) or a control virus at 3 months of age. Probiotic or control diets were administered at 9–12 months, with blood and fecal samples collected for ELISA and 16S rRNA gene sequencing. Behavioral assessments were conducted at 13–14 months, followed by analysis of brain inflammation, blood-brain barrier integrity, and GSK-3β activation. Rats expressing pseudophosphorylated tau displayed impairment in spatial Y-maze ( F 1,39 = 4.228, p = 0.046), spontaneous object location ( F 1,39 = 6.240, p = 0.017), and olfactory discrimination ( F 1,39 = 7.521, p = 0.009) tests. Phosphorylation of tau at S262 ( t 3 = -4.834) and S356 ( t 3 = -3.258) in the locus coeruleus was parallelled by GSK-3β activation in the hippocampus ( F 1,24 = 10.530, p = 0.003). Probiotic supplementation increased gut microbiome diversity ( F 1,31 = 8.065, p = 0.007) and improved bacterial composition ( F 1,31 = 3.4867, p = 0.001). The enhancement in gut microbiomes was associated with enhanced spatial learning ( p < 0.05), reduced inflammation indexed by Iba-1 ( F 1,25 = 5.284, p = 0.030) and CD-68 ( F 1,26 = 8.441, p = 0.007) expression, and inhibited GSK-3β in female rats ( p < 0.01 compared to control females). This study underscores the potential of probiotics to modulate the gut-brain axis and mitigate pretangle tau-related pathology in preclinical AD. Probiotic supplementation could offer a novel early intervention strategy for AD, highlighting the pivotal role of gut health in neurodegeneration.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".