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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 10

I personally download and listen to each of Come And Reason Ministries Bible study class lessons and PDF study notes to use when teaching my class. Really appreciate the class especially when Dr. Jennings is teaching. Thank God there are persons like him doing His work and traveling to share His beliefs.

B. L.M., North Plains, OR, USA

 

Testimony 72

I am blown away by the truth that you present. God’s Design Law makes so much sense! You have validated my impression that, if God is love, He would not kill those who don’t want to know him. If God gives us choice, then how can He destroy us if our choice is not to follow him. Thank you for opening my eyes and heart to the pure love of God seen through Jesus. The love I now have for Jesus is deeper and free from condemnation. My heart has been opened to love others as Jesus loves me. May God continue to bless your God-given insight into His word and your ministry. The truth has set me free!

H. Miller, Centereach, NY

Testimony 25

I just want to say thank you so much for your conversations via YouTube. I regularly tune in to your lectures, “Let’s Talk” sessions, and many others. Through these I’ve found greater depth and meaning to God’s word. Thanks for all that you do and please continue. I’m currently working in the middle of Silicon Valley at Stanford University. I feel like God really has me in the right place right now and I’m sensing that your teachings might be part of it.

B. F., Silicon Valley, CA, USA

 

Testimony 29

Thank you for all of your work to correct misconceptions about God’s character. So many people that my husband and I have talked to seem to be against the natural law construct and view it as “errant” and “dangerous.” Having learned more about it through your blogs and lessons, I don’t really understand why they view it that way, except that it means they have to relearn theology they have known for their entire lives. But I’m so excited to relearn this. For the past few years I have been questioning how I could trust a God who punishes arbitrarily and is full of wrath for those who don’t obey His commands. That view made me afraid to “mess up” or “not be good enough,” even within my relationship with God. I really appreciated the point you bring out about God not wanting us to serve Him because we are afraid, but because we love Him.

Melissa H., IN, USA

 

Testimony 59

I’m a native Ghanan, but am currently in France for my master’s degree. Prior to this, during my final years at undergraduate studies in Ghana, I was introduced to your ministry and I’ve been immensely blessed by what you share, especially about the Design and Imposed Laws. God richly bless you for that.

One of the first things I did when I arrived in France was to buy all four of your books. They not only helped me, but those I shared them with. I shared the message with an atheist student and I marveled at how God worked mightily in his life. Today this person shares the Love of God with others and debunks theories of who God is not. I want to share what you present in your “Heavenly Sanctuary and Investigative Judgment” pamphlet, because the message brought rest to my soul and I live today as a healthy person.

God bless you so much and your ministry.

Michael A., Ghana

 

Testimony 9

I really enjoy with you the view of a gracious God. Thank you for sharing the work you are allowing the Lord to do in you.

L., Queensland, Australia

 

Testimony 66

I am incredibly grateful for the transformative impact you’ve had on my life, and words cannot fully express my appreciation. Over the years, I have been an avid listener and follower of C&R and extend my heartfelt thanks for creating the C&R mobile app. It has allowed me to immerse myself in your lessons repeatedly, enabling me to grasp the profound significance about the Character of God, Design Law, the protocols for life, the reasons behind the current chaos, and Christ’s mission to restore everything. They have deeply touched me. Having studied with various churches, I came away with the perception that God is no different from the deities of ancient Greek or Roman mythology—demanding sacrifices and taking pleasure in bloodshed. Thanks to your transformative teachings, I have experienced a profound awakening to the true nature of God and the immense power of His love. It is truly a remarkable and liberating sensation to finally grasp the truth and embrace the empowering nature of God’s laws. My self-perception has become brighter and more infused with love. My journey of growth continues on a daily basis.

Chris P., Lake Mary, FL, USA

 

Testimony 44

We were given a gift of the DVD set, “God and Your Brain,” and we just finished watching it. The truths in this are so powerful and truly an answer to a prayer. We’re seeing hope where once we thought God wasn’t answering our prayers to be free of certain mindsets. He answered with these DVDs and we are hungry for more. Thank you!

Daniel T., Easley, SC, USA

 

Testimony 52

Your unique way in spreading the truth is what we all need today. Most of us don’t recognize the contamination coming from all the lies and selfishness in the world. Because of our fear of death, we forgot how to live. Lies left and right. I was losing hope and faith, because of so many ideas that are always contradicting each other – so many questions answered by other, more complicated, questions – until I found your channel on YouTube.

You did not just give me answers, you also taught me how to answer new questions that arise in my mind. Now I see things differently. I see God’s mercy, grace, and Love everywhere, in spite of all the chaos that we all have done as humans. I don’t fear death anymore. Accepting the Truth and Love about God is truly a genuine Freedom from all the confusions, sufferings, selfishness, pain, and death.

I just wanted to say, thank you, sooooo much for revealing the real Remedy for our infected life. I have a new hope and now see the world in a different perspective!

Wheinny P., University Place, WA, USA

 

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 69

After reading your book, ‘Could It Be This Simple,’ someone was explaining Christianity in a way that made sense to me for the first time in my life. One morning, I simply prayed “I’m sorry and I love you.” As soon as I silently said that, I could literally feel God’s presence and light flood down on me from above and fill me up with love and joy. I sat there crying my eyes out, because I was so overpowered with this feeling of love and joy. It was just so incredible. I hope that more people can read this book and get a blessing from it. It’s really amazing.

Rachael H.

Testimony 17

The blessings of clarity and understanding you and your class inspire me to take from the word of God have impressed upon me so greatly the true, loving character of our Creator. I have found amazing freedom and joy through building a stronger, more intentional relationship with Him. What is new is that this is now a relationship built on love, reverence and respect rather than fear and obligation, and as such my eyes have been slammed OPEN as I am continually impressed by the manifestations of God’s true character in His provisions for fallen man.

T.E.H., Salt Lake City, UT, USA

 

Testimony 16

Your seminars are still inspiring and changing our lives and we continue to share the principles we have learned from you. Your ministry has changed our lives!

E.W.

 

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

 

Testimony 49

I came into the church at 21, but that is as far as it went. I was so confused about what love is. I couldn’t find it in the bible, because I am not a person that can read between the lines. I have no logic. I have read many, many books; trying to figure out the crux of the matter. They were helpful, but something was still missing. I have become very frustrated to the point of crying out to God, “Where can I go?”  I needed some basics.

I found two books, written by Timothy Jennings, MD, to be very helpful. God showed me that I had lived my whole life in fear. I didn’t even see it. Now, I do. God is so good.  I discovered the “The Remedy”  Dr. Jennings new book, “The God-Shaped Heart!” Oh, I was so excited, I purchased them right away.

I can get rid of most of my books, because “The Remedy” brings the Love of God out so clearly, even I can’t miss it. Now, I want to sit and read my Bible. Wow, what a revelation! It is just simply Awesome! I am so grateful to Jehovah Almighty for hearing my prayer for more understanding! I am so encouraged!

Jackie S.