New genetics studies point to prevention for Alzheimer's in APOE E4
Hi everyone,
I recently saw a news article that called APOE E4 the "Chris Hemsworth gene". Like the "Thor" actor is the originator of knowledge about Alzheimer's genes :-)
In April, a study came out about genetic variants that gave protection against Alzheimer's in people with APOE E4. And then this weekend, a member sent me an article about a pre-print study that essentially replicated the first study's findings. It's always good when another group can replicate important findings.
My new article below explains the studies, the pathways involved, and some of the background science. I'm excited by the research, and not because I'm part of the 2% of people with the variant... Instead, I'm excited there is a clear, known pathway that can be targeted by diet and supplements (and likely by pharmaceuticals).
I encourage you to share the article with anyone interested in preventing Alzheimer's or other neurodegenerative diseases.
Stay curious,
~ Debbie Moon
Fibronectin, Genetics, and Alzheimer’s Prevention
Key takeaways:
~ Two new studies identify genetic variants in FN1, which encodes fibronectin, as being protective against Alzheimer’s in people with APOE E4.
~ Fibronectin interacts with amyloid-beta and the blood-brain barrier.
~ Variants that reduce fibronectin decreased Alzheimer’s risk by 70%.
Alzheimer’s pathology due to BBB dysfunction:
The biggest risk factor for late-onset Alzheimer’s disease is carrying an APOE E4 allele. For several decades, Alzheimer’s research has focused on preventing the buildup of amyloid-beta plaque in the brain. While amyloid-beta plaque clearly plays a role in the pathogenesis of Alzheimer’s disease, the drugs developed to block amyloid-beta haven’t helped much with Alzheimer’s symptoms. At best, they may slow the progression of the disease.
Amyloid-beta plaques are thought to be deposited in response to activation of microglia (cells of the brain’s immune system). Inflammation and oxidative stress in the brain activate microglia. But another part of the picture in Alzheimer’s pathology is changes in the blood vessels – the cerebral vasculature and the blood-brain barrier.
Recently, two large studies of the interaction of APOE E4 with other genetic variants have shed light on how changes in the blood vessels and the blood-brain barrier are important for the buildup of amyloid-beta plaques.[ref][ref]
Both genetic studies found that variants that reduce fibronectin significantly decreased the risk of Alzheimer’s in people with APOE E4 genotypes. The variants identified were not very common (around 1-2% of the population).
Personally, I’m excited about this research, not just for the 1% of people with the variant, but because it strongly suggests what goes wrong in the brain to cause Alzheimer’s. Most importantly, this is a potentially modifiable pathway.
Let’s look at what’s going on with fibronectin, the blood-brain barrier, and Alzheimer’s. Then I’ll include the variants in the genotype report that are associated with reduced Alzheimer’s risk in APOE E4 carriers.
New on Longevity Lifehacks:
TNF-alpha and Inflammaging
My latest Longevity Lifehacks article is on reducing TNF-alpha to prevent damage due to excess inflammation in aging.
"TNF-alpha (tumor necrosis factor alpha) is a proinflammatory cytokine that is usually upregulated in aging. TNF-alpha acts as a signaling molecule in our immune system and is important in our innate immune response. However, chronically elevated TNF-alpha is one cause of the diseases of aging. Inhibiting chronic inflammation is one tool available for longevity and healthspan."
What I've been reading:
1) Gene-expression profiling of individuals resilient to Alzheimer's disease
Another new study looks at people who don't get Alzheimer's even with amyloid-beta in the brain. This study examined the protein expression in resilient brains and found that metallothionein proteins and heat-shock proteins were increased in resilience. Metallothioneins help to detoxify heavy metals, and the researcher found that they were higher in the astrocytes, resulting in less inflammation and oxidative stress.
2) No Inner Voice? New Study Reveals Its Impact on Memory
This article explains a new study on people who lack an inner voice, which is called anendophasia. People who lack an inner voice have a harder time remembering words and rhymes, but they also use different strategies for problem-solving.