HoldsUp

Jack Auty

Dr. Jack Auty is a researcher based in Tasmania who focuses on brain health and inflammation. His work investigates the role of inflammatory mechanisms in diseases such as Alzheimer's disease. Additionally, his research explores potential contributors to inflammation, including zinc deficiency and microplastics.

24 claims checked on air: 1 context 1 contradicted 4 overstated 14 supported 4 unverified

What they said on air - supported

0:04:12supportedhighLooking At Microplastics & Inflammation’s Impact on Brain He

Cannabinoids suppress the immune system and operate primarily through two receptor types: cannabinoid receptor type 1 predominantly on neurons, and cannabinoid receptor type 2 predominantly on immune cells.

"marijuana-like substances, they uh actually are anti-inflammatory, they suppress the immune system and they work through two the cannabinoids. Marijuana-like substances work through two main receptors. One is predominantly on neurons and that's what causes the getting high effect of marijuana and the other one is actually predominantly on immune cells um and that's called cannabinoid receptor type 2." (said at 0:04:12)

The speaker's statement accurately reflects standard endocannabinoid pharmacology and immunology. Cannabinoids exhibit anti-inflammatory and immunosuppressive properties. They act primarily through two canonical G-protein coupled receptors: cannabinoid receptor type 1 (CB1), which is predominantly expressed in the central nervous system on neurons and mediates the psychoactive effects of cannabis, and cannabinoid receptor type 2 (CB2), which is predominantly expressed on immune cells and mediates immunomodulatory and anti-inflammatory actions.

0:06:12supportedhighLooking At Microplastics & Inflammation’s Impact on Brain He

The CRASH trial evaluating corticosteroid anti-inflammatories for head injury found an absolute increase in death rate of 3.8% compared to placebo.

"This was sort of reinforced in a very famous clinical trial called the CRASH trial. Now, the CRASH trial was actually on head injury, not stroke, but it's a similar theory. If you whack your head, your brain swells up, we need to suppress that immune system and they were using a much more potent and broad-spectrum anti-inflammatory, steroid-based um anti-inflammatories, uh but they found uh an absolute increase in death rate of 3.8%" (said at 0:06:12)

The MRC CRASH trial was a large, multicenter, randomized controlled trial of 10,008 adults with significant head injury comparing a 48-hour infusion of corticosteroids (methylprednisolone) against placebo. The trial was stopped early after demonstrating a significant absolute increase in mortality in the corticosteroid group: 14-day all-cause mortality increased by an absolute 3.2% (21.1% vs. 17.9%, relative risk 1.18, 95% CI 1.09–1.27), and 6-month mortality increased by an absolute 3.4% (25.7% vs. 22.3%, relative risk 1.15, 95% CI 1.07–1.24). The speaker's description of the trial design and findings closely matches the published trial results.

0:06:59supportedhighLooking At Microplastics & Inflammation’s Impact on Brain He

Neutrophils release the enzyme myeloperoxidase (MPO), which produces hypochlorite (bleach) outside the cell, as well as proteases.

"there's an immune cell in your blood called neutrophils. It's the most common immune cell in your blood and they are just packed full of broad damaging enzymes and molecules. So, they would release an enzyme called MPO that actually produces, once it's out of the cell, it produces bleach, uh hypochlorite. It actually generates bleach, these neutrophils. Um they also produce enzymes that chop up everything, proteases that chop up everything in the brain." (said at 0:06:59)

Neutrophils are the most abundant circulating white blood cells in humans and store large amounts of myeloperoxidase (MPO) and proteolytic enzymes (such as neutrophil elastase, cathepsin G, and matrix metalloproteinases) in their granules. Upon activation and degranulation, released MPO catalyzes the reaction between hydrogen peroxide and chloride ions to generate hypochlorous acid (HOCl, the active component of household bleach) and hypochlorite. Both MPO-derived HOCl and neutrophil-secreted proteases degrade extracellular matrix components, proteins, and surrounding tissues during inflammatory responses.

0:15:48supportedmoderateLooking At Microplastics & Inflammation’s Impact on Brain He

Postmortem examinations show that around 70% of Alzheimer's disease cases have vascular pathology contributing to the disease.

"studies have now shown, you know, around about 70% of Alzheimer's disease once you actually look postmortem have vascular pathology contributing to it." (said at 0:15:48)

Postmortem and clinicopathological cohort studies consistently demonstrate that pure Alzheimer's disease pathology is relatively uncommon in late life, with the majority of clinically diagnosed Alzheimer's cases exhibiting mixed pathologies—most frequently cerebrovascular lesions (including cerebral amyloid angiopathy, cerebral infarcts, arteriolosclerosis, and microbleeds). Neuropathological series report that approximately 50% to 80% (frequently cited around 70%) of postmortem Alzheimer's cases exhibit co-existing vascular brain injury contributing to cognitive decline.

0:24:20supportedlowLooking At Microplastics & Inflammation’s Impact on Brain He

Amyloid aggregates have been shown in laboratory studies to create holes in bacterial cell membranes, leading to the hypothesis that amyloid functions as an antibacterial protein.

"amyloid has been shown to create holes in the membranes of bacteria. And so some people conclude that um amyloid might be an anti- antibacterial protein." (said at 0:24:20)

Laboratory and preclinical studies demonstrate that amyloid-β (Aβ) functions similarly to antimicrobial peptides by targeting microbial cell membranes, forming pores/membranolytic structures, and entrapping pathogens. In vitro assays show Aβ exhibits potent antimicrobial activity against diverse bacteria and fungi, leading to the hypothesis that Aβ plays a functional role in innate immunity.

0:24:35supportedvery lowLooking At Microplastics & Inflammation’s Impact on Brain He

Amyloid aggregate exposure to cell membranes induces ion transportation such as calcium influx into neurons.

"if you drop a little bit of amyloid on a membrane, we see a transportation of ions through the membrane that shouldn't normally happen. So, calcium flux might happen if you drop a tiny amyloid, like a really tiny amount of amyloid on a neuron, we'll see calcium move into the cell, which we don't normally do. So, it's obvious that the amyloid has made a small hole in the membrane." (said at 0:24:35)

Biophysical and cellular studies demonstrate that amyloid-beta (Aβ) oligomers interact directly with plasma membranes to form multi-subunit pores or membrane perforations. These pores permit uncoordinated ion transport across cell membranes, resulting in intracellular calcium influx and increased electrical conductance in neuronal cells. Certainty is graded as very low because the supporting evidence is derived entirely from in vitro biophysical models, synthetic lipid bilayers, and cellular/animal neuronal assays.

0:25:15supportedvery lowLooking At Microplastics & Inflammation’s Impact on Brain He

Michael Heneka's research demonstrated that deleting the NLRP3 gene in an Alzheimer's mouse model resulted in almost no cognitive decline in the mice at that stage.

"Michael Heneka's one of them who's deleted the NLRP3 gene in mice and then crossed that with an Alzheimer's mouse model. And what he found was almost no cognitive decline in those mice at that time point." (said at 0:25:15)

In a landmark 2013 study published in Nature, Michael Heneka and colleagues demonstrated that crossing an NLRP3 knockout mouse (Nlrp3-/-) with an APP/PS1 transgenic mouse model of familial Alzheimer's disease largely protected the mice from spatial memory deficits, long-term potentiation impairment, and amyloid-beta pathology. Because this evidence is derived exclusively from transgenic animal models, the GRADE certainty is rated very low.

0:27:10supportedhighLooking At Microplastics & Inflammation’s Impact on Brain He

Inhaling cut stone crystal powder (silica) triggers massive inflammation through NLRP3 activation and causes silicosis.

"which is essentially a fine crystal powder silica. Which causes a disease called silicosis. If you ever breathe in cut stone, that causes massive inflammation in the body. So, if you're ever cutting stone with an angle grinder, please wear a mask. It can absolutely kill you. Anyway, that's the positive control for NLRP3 activation" (said at 0:27:10)

Crystalline silica inhalation (such as dust generated from cutting stone or engineered stone products) is an established cause of silicosis and is widely used as a prototypical activator of the NLRP3 (NALP3) inflammasome. Inhaled silica particles engulfed by alveolar macrophages cause lysosomal destabilization and reactive oxygen species generation, driving NLRP3 inflammasome assembly, caspase-1 activation, and the secretion of pro-inflammatory cytokines such as IL-1β and IL-18, which triggers chronic pulmonary inflammation and progressive fibrosis.

0:30:12supportedvery lowLooking At Microplastics & Inflammation’s Impact on Brain He

Young birds that had ingested plastic exhibited a dementia-like molecular signature compared to control birds, with BDNF levels reduced by approximately half.

"these were young birds, but the young birds with plastic had a dementia signature compared to the young birds that hadn't eaten any plastic. And one of the key uh proteins that was identified that generated the signature was BDNF. And the BDNF levels were actually half of the control birds" (said at 0:30:12)

A 2025 proteomic study in young, wild shearwater chicks (<90 days old) found that birds with high levels of ingested plastic exhibited blood proteomic profiles indicative of neurodegenerative disease compared to controls, with marked downregulation of key neuroprotective proteins including brain-derived neurotrophic factor (BDNF). Because this is an observational study in wild non-human animals, the certainty of evidence for broader neurodegenerative implications in humans or other species is rated very low.

0:37:51supportedvery lowLooking At Microplastics & Inflammation’s Impact on Brain He

Zinc depletion in innate immune cells like macrophages and microglia activates the NLRP3 inflammasome and triggers IL-1 release.

"he found that if you depleted the zinc from an immune cell and a an innate immune cell like a macrophage or a microglia, they became hypersensitive. And they became inflammatory, in fact. You could actually if you depleted them enough of zinc, the NLRP3 receptor would activate and you'd get IL-1 release." (said at 0:37:51)

In vitro experimental research confirms that zinc depletion in innate immune cells (such as macrophages) triggers the activation of the NLRP3 inflammasome and leads to the processing and secretion of interleukin-1beta (IL-1β). Because the evidence is derived from preclinical in vitro cell models, the GRADE certainty is very low.

0:40:02supportedlowLooking At Microplastics & Inflammation’s Impact on Brain He

Analysis of the ADNI cohort showed that individuals taking zinc supplements had a significantly slower rate of cognitive decline over a 10-year period.

"For the clinical data, I looked at people who were enrolled in a a cohort called the ADNI cohort... And what it turned out was the people that were taking zinc supplements had a significantly slower cognitive decline over that 10-year period." (said at 0:40:02)

Analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort published by Rivers-Auty and colleagues (2021) showed that reported zinc supplementation was associated with a significantly reduced rate of cognitive decline and lower disease progression in individuals with mild cognitive impairment and Alzheimer's disease. Because this clinical finding comes from an observational cohort study rather than a randomized controlled trial, the certainty of evidence for therapeutic efficacy is low.

0:42:05supportedvery lowLooking At Microplastics & Inflammation’s Impact on Brain He

In mouse models genetically engineered to develop Alzheimer's disease, zinc deficiency accelerates cognitive decline, whereas knocking out NLRP3 reduces sensitivity to zinc deficiency.

"these mice are genetically engineered to get Alzheimer's disease, and it turns out if you make them zinc deficient, they get it much faster. They get the cognitive decline much faster. And what was interesting is if you knock out NLRP3, they're less sensitive to being zinc deficient" (said at 0:42:05)

A 2021 study published in The Journal of Neuroscience examined the effect of zinc deficiency in the APP/PS1 transgenic mouse model of Alzheimer's disease. The authors found that zinc-deficient diets accelerated Alzheimer's-like cognitive/memory deficits, and that genetically knocking out NLRP3 protected APP/PS1 mice against this accelerated cognitive decline. Because the findings are based on animal and in vitro models, the GRADE certainty is very low.

0:44:04supportedmoderateLooking At Microplastics & Inflammation’s Impact on Brain He

Age-adjusted incidence rates of Alzheimer's disease among 75- and 80-year-olds have been declining over the past two to three decades.

"the number of 80-year-olds with Alzheimer's disease is going down. The number of 75-year-olds with Alzheimer's disease is going down. So, while our diet is getting worse and our exercise is getting worse, for some reason uh Alzheimer's incidence is going down if you adjust for age." (said at 0:44:04)

Multiple large, long-term prospective cohort studies in the United States and Europe have demonstrated that age-adjusted incidence rates of dementia and Alzheimer's disease have steadily declined over the past 25 to 30 years. For example, data from the Framingham Heart Study demonstrated a 44% reduction in the 5-year age- and sex-adjusted cumulative hazard rate of dementia across four consecutive epochs spanning the late 1970s to the early 2010s. Similarly, a pooled analysis of seven population cohorts across Europe and North America (the Alzheimer Cohorts Consortium) found that the age-specific incidence rate of dementia declined by approximately 13% per calendar decade between 1988 and 2015.

0:47:48supportedhighLooking At Microplastics & Inflammation’s Impact on Brain He

In the 2-year Finnish Geriatric Intervention Study (FINGER trial), multidomain lifestyle intervention produced a modest, statistically significant improvement in cognitive function.

"the FINGER trial... It's the Finnish lifestyle trial. And so, for 2 years, these people had they had nutri uh weekly meetings with dieticians, and they had personal trainers given to them, and they're over 65. And what they saw was a very tiny, kind of disappointing, but a a tiny improvement in cognitive function over 2 years." (said at 0:47:48)

In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomized controlled trial involving 1,260 older adults (aged 60–77 years) at elevated risk of dementia, a 2-year multidomain lifestyle intervention (dietary counseling, physical exercise, cognitive training, and vascular risk monitoring) resulted in a modest, statistically significant improvement in overall cognitive performance compared to standard health advice. The estimated 2-year mean change in comprehensive neuropsychological test battery (NTB) total Z score was 0.20 in the intervention group compared to 0.16 in the control group (between-group difference in annual change = 0.022, 95% CI 0.002–0.042, p = 0.030).

Fact-checked episodes

Publications

No PubMed publication profile has been built for this speaker yet.