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Alzheimer’s, Cholesterol, and Genetics – How to Reduce Your Risk for Dementia

Alzheimer’s, Cholesterol, and Genetics – How to Reduce Your Risk for Dementia

It has been known for more than two decades that elevated cholesterol was associated with increased risk for Alzheimer’s Disease (AD).[1] It is also known that the ApoE gene produces a protein that transports fats, including cholesterol, into brain cells.

In the human population, there are three variants of the ApoE gene. Seven percent of the population has ApoE2, which confers increased risk for atherosclerosis; 79% has ApoE3, which confers no disease risk; and 14% of the population has the ApoE4 variant, which increases the risk for AD.

But, not everyone with either the ApoE4 gene or elevated cholesterol gets AD. Could there be an interaction between the higher concentrations of cholesterol and a specific ApoE gene variant that does increase the risk? The answer seems to be yes. Research has demonstrated that modulation in cholesterol alters the ApoE gene activity.[2] Further research has discovered a nexus between these two factors. A high-fat diet was demonstrated to increase insulin resistance and cognitive decline in all groups, whether ApoE4 or ApoE3. However, those with the ­ApoE4 gene had “exaggerated” deficits in the part of the brain specific to new learning and forming new memories in the hippocampus, but when those with the ­ApoE4 gene were placed on a low-fat diet for one month, all deficits reversed and learning and cognitive function returned to normal![3] The researchers concluded that those with two copies of the ­ApoE4 gene were particularly susceptible to neuronal and cognitive impairments due to insulin resistance caused by a high-fat diet.

Having demonstrated that low-fat diets result in improved cholesterol profiles and subsequent improvement in brain and cognitive function — especially in those with two copies of the ApoE4 gene, researchers examined whether cholesterol lowering medications could offer the same benefit. Data from long term clinical trials have demonstrated that some, but not all, cholesterol lowering medications conferred reduced risk of AD and better cognitive performance, especially in those with two copies of the at-risk ApoE4 gene. The greatest positive effect was seen with atorvastatin (P = .026) and the least with lovastatin (no significant difference found). Those individuals with two copies of the at-risk gene and who already had symptoms of AD, but received statin medication, had significantly better cognitive function over the course of a 10-year follow-up, compared with those who did not receive the statins (P < .01).[4]

Recently, researchers from Johns Hopkins University have discovered another brain protein that appears to be involved and works in concert with elevated b-amyloid to cause the cognitive and memory impairments of AD. The NPTX2 gene is one of the first genes to get activated when new memories are forming. If you are trying to remember what you are reading in this article, then normally NPTX2 would activate and produce the protein with the same name (NPTX2). This protein acts as an instigator and activator of synaptic signaling and neural circuit recruitment, critical in the formation of new memories. Without this protein, the neural circuits cannot effectively synchronize to form new memories. When this gene is turned down at the same time b-amyloid is building up in the brain, the neural circuits’ ability to adapt and organize is impaired, contributing to the cognitive and memory decline of AD. Individuals with high b-amyloid and high NPTX2 did not show cognitive changes of AD, and individuals with low NPTX2 and low b-amyloid also did not show impairment of cognition and memory. This study documented that both high b-amyloid and low NPTX2 were required for the negative outcomes. The good news is that the cause of suppressing NPTX2 is different than what causes elevations in b-amyloid.[5] This provides additional opportunities to make lifestyle changes to protect our brains and prevent dementia — even if one has the at-risk genes.

So, what turns on the NPTX2 gene? Activity of the neurons themselves![6] Staying mentally engaged and cognitively active — people who are lifelong learners — keep the neurons active and NPTX2 turned on, with reduced risk of AD. Additionally, externally firing the neurons with treatments such as electroconvulsive therapy has been documented to increase the expression of this gene.[7] These two findings makes it likely that any activity that increases the neuronal firing will activate the NPTX2 gene and may be one of the benefits of transcranial magnetic stimulation, which causes neuronal firing via magnetic waves rather than electrical pulses.

Not only does NPTX2 enhance learning, neural circuitry recruitment, synchronicity, and brain neural plasticity, it also modulates a receptor (AMPA) involved in non-programmed cell death. Therefore, while normal amounts of NPTX2 are neural protective, and low amounts increases the risk of dementia, significantly higher than normal activity of NPTX2 can trigger AMPA and instigate unscheduled cell death. This, unfortunately, appears to occur in persons with Parkinson’s disease and Lewy Body dementia, where NPTX2 is increased by more than 800% in the motor pathways.[8]

Another protein critical in maintaining brain health is repressor element 1-silencing transcription (REST) factor. REST functions within the cell like a conductor of an orchestra, directing various genes to sound out (express themselves) or be silent (turn off). As a result, REST is involved in determining how neurons develop, what function they fulfill, their connections and networking to other neurons, and, as expected, is highly active in childhood during the massive remodeling of brain development.

In the past, it was believed REST became inactive after a person reached adulthood. However, recent research has discovered REST is active in older brains and functions to protect the memory circuits (hippocampus) from damage due to hyperexcitation and plays a key role in protecting the brain from damage associated with aging. Reduced levels of REST are associated with loss of brain volume in the hippocampus (memory circuits) and increased cognitive impairment. In persons who have the toxic build up of protein associated with Alzheimer’s dementia (amyloid and tau), those with high REST activity did not demonstrate cognitive decline or progress to dementia, supporting the idea that REST is neural protective. The critical question: What affects the availability of REST? Chronic mental stress suppresses REST, contributing to accelerated aging and cognitive decline, whereas meditation, that reduced stress, is associated with increased levels of REST and subsequent brain health. [9]

With all of this in mind, genetics appears to account for about one-third of the risk of developing AD. What is the key then that contributes to developing AD, if it isn’t simply genetics? Strong evidence points to inflammation, which contributes to insulin resistance in the brain, that causes a cascade of events, resulting in the death of brain cells and the development of AD. Exercise, along with most of the other modifiable factors (sufficient sleep, anti-inflammatory diet, stress management, etc.), reduces inflammation and insulin resistance, keeps neurotrophins (proteins that act like fertilizer for the neurons), REST, NPTX2, and other protective factors turned on, thereby preventing the development of AD.

While aging is inevitable, dementia is not! We can make choices to protect our brains and prevent the development of late-life Alzheimer’s dementia. I recommend my new book, The Aging Brain: Proven Steps to Prevent Dementia and Sharpen Your Mind, which is an integrative examination of the various contributing factors to AD and outlines a comprehensive action plan to slow the aging process and keep our brain healthy.


[1] Jarvik GP, et al. Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: a case-control study. Neurology. 1995;45(6):1092–6.

[2] Petanceska SS, et al. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci. 2003;20(3):395–406.

[3] Johnson LA, Torres ER, Impey S, et al. Apolipoprotein E4 and insulin resistance interact to impair cognition and alter the epigenome and metabolome. Sci Rep. 2017;7:43701

[4] Geifman N, Brinton RD, Kennedy RE, et al. Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease. Alzheimers Res Ther. 2017;9:10.

[5] Xiao MF, Xu D, Craig MT, et al. NPTX2 and cognitive dysfunction in Alzheimer’s disease. eLife. 2017 March 23;6.

[6] Reti, IM, et al., Prominent Narp expression in projection pathways and terminal fields. J Neurochem. 2002 Aug;82(4):935-44.

[7] Reti, IM, Baraban JM, Sustained Increase in Narp Protein Expression Following Repeated Electroconvulsive Seizure, Neuropsychopharmacology (2000) 23, 439–443. doi:10.1016/S0893-133X(00)00120-2

[8] Moran, LB, et al., Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodies, Acta Neuropathol. 2008 April; 115(4): 471–478.

[9] Ashton N, Hye A, Leckey C et al. Plasma REST: A Novel Candidate Biomarker of Alzheimer’s Disease Is Modified by Psychological Intervention in an At-Risk Population. Transl Psychiatry. June 6, 2017; 7(6): e1148

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Testimony 65

I have been tuning into your weekly study classes for a while now and wanted express my appreciation for the teachings that ha been a huge blessing in opening up the true message of the word. Viewing scripture under an imposed law theory always, without fail, raised more questions, concerns, and conflicting scripture interpretations that were discouraging at the very least. Looking at scripture through the design law lens has brought more truth to light for me personally and an understanding of our Heavenly Father that places Him “above all others,” where I am now more than thrilled to witness and serve Him.  I “stumbled” across this ministry a year or so ago and would only watch a few minutes at a time. But the more I listened and the longer I paid attention, the more my spiritual eyes were opened to the ever present truths of scripture. The comprehension of the great controversy and it’s origin by the lies perpetrated and perpetuated throughout the Bible on the attack of God’s character and government is truly priceless. Keep up the Good Work! Your servanthood is desperately needed in such a time as this!

Jeff D., Reading, MA, USA

 

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Just watched watched lesson 10 in the 1st quarter 2021 bible study classs on Isaiah. I want to thank you for your intellectual spirituality; it’s not an oxymoron! From the point of view of a teacher I also enjoy seeing how much personal pleasure you clearly take in not just tasting, but feasting on God’s word – it reminds me of Jeremiah not being able to hold it in! It makes me smile that your cup is so full and overflowing that you make it to Tuesday’s lesson (on a good day). It just goes to show the richness of God’s Word.

God bless the Come and Reason Team from our church here in Great Britain.

Andrew H., Great Britain

 

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Testimony 63

I’ve been very blessed by “The God Shaped Brain” and this ministry, through video and podcast, over the last few years. It’s truly opened up my eyes more to the truth about God and the importance of that truth in the present world. The message is so inviting, freeing and enlightening and MORE people need to know about it. I believe it is the last message that can truly, not only prepare a people for salvation and translation, but vindicate the character of God.

Michael V., Yonkers, NY, USA

 

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I have been watching your videos in The Power of Love seminar and I must say these have liberated me and have improved my relationship with the Lord. I am no longer terrified of him as I was before following your teachings.

Thando N., South Africa

 

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S. G., TX, USA

 

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I am absolutly on fire with the message at Come and Reason! I can’t get enough! I’ve read your book, blog, and articles. I’ve listened to your Bible study podcasts, your radio show, and your series – all excellent! It wasn’t until the past couple of years that I have I like I’m becoming “healthy,” with more to share with others than just beasts and commandments! I used to be a Bible worker and preached when the pastors were gone until I had had enough. I didnt realize at the time what the problem was, but i know now… the message wasn’t properly focused. Now my flame is rekindled. All of your little examples are so perfect in explaining something “complicated” and making it easily understood! Now I’m trying to shape it into a life changing evangelistic series! Thank you!

M.T., USA

 

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Your teachings about our heavenly Father have changed my life. Thank you sooooooo very very much! I know He’s doing some serious healing in my heart and life and I look forward to each new day to learn something new about Him and to just hear you speak about Him. Thank you, forever.

Nancy S.

 

Testimony 39

[This ministry is the] biggest blessing I have ever received! Your DVDs and lessons could not have come at a better time in my life. I have experienced in the past year many difficulties that, if it wasn’t for this wonderful view of God that I have discovered through this ministry, I would not have been able to respond in love and forgiveness. My heart is being transformed everyday by the Calvary-looking God you teach. Hallelujah!! I have tears in my eyes as I write, because my life has taken a complete turn from where I was heading.

I am from Central America. Most of my family is scattered in different parts of the world and all have the same view of God that I had growing up; a distant, exacting, and ready-to-punish-us-with-tragedy type of God. So, I have been translating lessons for my family and, to my surprise, they have also been sharing them with others! I can already see the difference. My brother has often said, “Thank you for sharing, I have never heard it this way!” My other family members are taking an amazing turn from a message of “repent or burn” towards a loving God, pleading to us that we won’t reject him because he loves us eternally.

Bless you for all you do.

Sofia S., Ashfield, MA, USA

 

Testimony 54

I had a lot of pressure, as a pastor’s kid, to conform and be “good.” I was good at being “good.” I thought my life was going along well until it all started falling apart and I could not figure out why! In my search for “why is this happening to me, God?” I came across your book, “Could it be this Simple,” and God started revealing to me the many distortions I held about His character, His principles, and how He has designed His universe to operate. I remember thinking, “Wow, I have had this all backwards.” I was happy and angry all at the same time. Happy to have the light of truth break through the darkness, revealing a wonderful, beautiful way of understanding God and His plan for His children, and angry, because I felt deceived and cheated by the church, my family, and myself!

My heart thrills when I listen to your bible study lessons. Literally I have gone from death to life. It is a journey I look forward to every day, as God reveals areas this distortion affects. Praise GOD! I will ever be grateful to God for this ministry and your cooperation with the Spirit!

Karen S., Portal, AZ, USA

 

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The Healing the Mind DVD set tarted me on a journey that has changed my relationship with our loving God more significantly than any other study, and brought me to your book and Bible study podcasts, which I now listen to daily, thanks to the availability of archived content on your site and on iTunes.

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Testimony 38

Since November 2015, when I started studying Gods word from this God Is Love point of view, my life has been transformed. My troubled marriage of 15 years has been healed and my husband and I are truly happy for the first time in 15 years. Now When I read the word of God I understand it so much better and I can’t help but see Gods love radiating through the pages to humanity. Gods word is living and active and I am blessed beyond measure to be having this amazing experience. God has given me a beautiful understanding of Jn 3:16 that amazes me more and more each day. Thank you again for your ministry.

Helen D., London, England

 

Testimony 32

The message [of Come And Reason Ministries is] for all Christians (and those who may become Christians) and not just Adventists or any other group. It is difficult to imagine why any [anyone] with intellectual and spiritual honesty could find fault with the way you explained the healing substitution concepts and the truth about God’s character, though I know some will reject and criticize. On behalf of those in our group near Tacoma, WA, thank you and your staff for all of the hard work and for sharing the Gospel in this manner. God’s message of healing love will be carried to the whole world and then Jesus will come – He promised it.

Terry U., Tacoma, WA, USA

 

Testimony 43

Two years ago I stumbled upon your book, “Could It Be This Simple,” and then found “The God-Shaped Brain” videos on YouTube, your bible study class, and the ‘Come And Reason’ mobile app. I shared your book with a friend and after nine months of showing love, patience, and kindness this person has been changed by the love of God, too. The same love that healed me, I now express to other women in tangible ways, such as to a Baptist woman with high anxiety and childhood trauma. She was extremely happy and relieved when I shared about the so-called “judgment of God” and burning in hell. She had no desire to serve a God that was so harsh. I have repeated the phrase dozens of times to her. “What we believe has power over us, but we have power over what we believe…”

This message that you are sharing has changed my life. I will continue to serve other women and bring this message of God’s healing love to their lives by sharing your books, YouTube videos, and The Remedy Bible app. Keep up the good work. Don’t be discouraged. God is doing a mighty work in and through this ministry!

Jill L., Midwest, USA

 

Testimony 64

I’ve been reading the bible and walking with Jesus since I was around 16. I’m 42 now. I’ve mostly been alone in my walk although I went to several churches in different denominations. For the past 3 years God has been showing me His character of agape. It’s been a blessing and changed how I view God and my walk with Jesus. About a year ago I came across the power of love and the principles of design law. These teachings changed how I read scripture and have been such a beautiful blessing. I’m very excited and grateful for these truths. We share these truths of agape, design law and the reality of the principles of the two trees in the garden of Eden with people on Facebook and YouTube. People all over are learning to trust God and His agape design law which makes life possible. Thank you for everything you shared with me. May God continue to bless your ministry and lives.

Bradley M., Hinsdale, NY, USA