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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 36

Thank you and may God continue to bless you as you share with others the intricacies of how we are all “fearfully and wonderfully made”. I must share that you have opened a whole new world to me, and I have found tremendous healing through what you have shared in two of your books, “Could It Be This Simple?” and “The God Shaped Brain.” I praise God for what you shared, what I have learned, and how I have grown and healed! My prayer is that My Precious Jesus will be seen by others in the way I live, act, talk, etc. and they may be encouraged to know He is truly a GREAT God of LOVE, desiring that no one should perish! God Bless you in your continued endeavors to present Him as He really is!

Joleen H. GA, USA

 

Testimony 21

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

 

Testimony 40

I was brought up in a different faith and have been petrified my whole life of God. I believed that I would burn in hell for eternity. When I was 12 I started pursuing the things of this world, but for the next 45 years the Spirit was always calling me, as I knew there was a God through nature. I could see the vast sea of stars in the universe and knew there was something bigger out there. Five years ago, through a Revelation seminar, I was blessed to learn about God’s character and government.

Then I found Come and Reason Ministries and have come under some extreme pressure when I speak about the ministry. One time a member sent me an internet article titled “Whats wrong with Tim Jennings?” I asked her what she thought of it and she said “I don’t know, I didn’t read it.”

I have always wanted to find out for myself the truth about God, so I stayed with the Design Law construct and have been liberated to understand the big picture. Once we consider Design Law, all other Bible stories and prophecies seem to fit perfectly. It is truly beautiful to see people grasping how God operates this Universe of Love and the liberation it has provided in their lives. It blows my mind to see how consistent Design law is with what our founders believed. I hear statements like “This makes so much sense.”

Tom W., Mt. Pleasant, MI, USA

 

Testimony 53

I was so blessed by a friend who gave me your book, “The God Shaped Brain,” while I was sitting in church asking God to please help me learn more about Him and help me not to be so confused and scared. That was about 2 years ago. Your books have helped me to love God even more. I’m not confused or scared anymore! I have listened to all of your bible study classes and feel like I know the wonderful people that attend every week. Thank you for all that you’re doing in spreading the true message about God and His law of love. God bless you and your whole class.

Elssy P., Modesto, CA, USA

 

Testimony 45

I have been confused for years about what [christianity] calls [its] most disgusting teaching. It has never made much sense to me and for that reason has been evermore empty. I have listened to your class off and on and have struggled determining what is truth, because of the resistance design law encounters in the church. So, I thank God for your ministry. What you teach makes sense. It’s logical and backed up by the power of love. I have never seen that in Christ until now. I am astounded by the insight that is found when we look at God’s ministry through design law. All strength to this message, as I believe it to be the power of God.

Brendon S.

 

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 61

I grew up in a prominent protestant church and had what I like to call religious anxiety. I’ve always had questions about God and Salvation that no one could seem to answer.  I didn’t know how to find resolution. During 2020, at the height of my anxiety, I fell to my knees and begged God to show me truth and light and to give me the hope that I’ve been longing for. Days later, I stumbled upon your online videos and it was like a veil was lifted and EVERYTHING made sense! For the first time in my almost 39 years of life, my religious/spiritual anxiety has lessened. I feel a sense of freedom and peace I’ve NEVER had before… and it’s all because my view of God has changed. Thank you!

Ashleighn C.

 

Testimony 57

You have helped make sense of thirty two years of confusion. The material you freely provide reorganized so much of my life into such a beautiful pattern that has always been hinted at from within, but misguided with my training and what I was experiencing externally. My filipno parents, who were converted from Catholicism to SDA, were sincere and did their best to raise me the right way and I have deep respect for them. However, being immigrants and not understanding the language made for a difficult transition as I was growing up, which also applied to my spiritual growth as I learned the patterns of religion. I have been listening to as many bible study classes and reading blog posts as my time in a work truck will allow, searching for the practical applications of where spirituality and reality meet, and I thank you for helping me find that. You have helped me reach a point in which I can truly say that I love God, that I believe He loves me, and, like David, I delight in His law. God bless.

Emmanuel V., Calgary, AB Canada

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 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 28

I have been following your Bible study class for about a year now. I must say I am impressed with how your ministry has grown. I took it upon myself to listen to all your lesson podcasts from the past and they have both enriched me physically, mentally, emotionally and spiritually. I have learnt a lot from this class. I have also noticed how the class has grown in spiritual strength. One of the things that benefited me is that now I am not afraid of God. I use to be, but now it has melted away. The second thing is that you helped me to have a real life relationship with God. Now He is my friend that was always there and I love having him with me all the time. Thirdly, because of this class, it inspired me to take over and lead a class. I have called it “Let Us Reason Together,” adapting your inquisitive style and creating a class of free thinkers.

T. Banda, Malawi, Africa

 

Testimony 6

I got the book “Could It Be This Simple?” a few months ago and the reading was wonderful and I was fascinated. I lent the book to a friend at work. She is having a difficult time and the book is helping her to find Jesus and I found this very exciting. She has asked me questions and I can see her life changing.

H. S., Australia

 

Testimony 67

I was introduced to Come And Reason by a friend of my mother-in-law, who gave me several CD’s of Dr. Jennings. The clarity of the message and recognition that God’s is a God of love was so clear, advancing beyond Dr. Maxwell’s message. However, grappled with Maxwell saying God used emergency measures for the fallen world. Now after several years of being a regular listener of the Come And Reasoning bible study class and attending Jennings’ meetings in Dallas/Fort Worth, TX, things are becoming clearer for me. Design law versus imposed law has added so much to my personal understanding of theology. This message has really impacted my work in counseling so many people miserable because they are searching for and trusting human governments to create order and peace or believing in a God who says love Me or I will kill you. I am grateful that I have an alternative view to offer my clients that makes sense. I teach a bible study class on a semi-regular basis and I value the materials that Come And Reason so freely offers to aid me in presenting this vital message. Thank you for continuing to provide advancement in our very limited understanding of a Infinite God that is rational and believable.

Dr. Roger D, Arlington, TX, USA

 

Testimony 30

God lead me to your book “The God-Shaped Brain” while I was searching for another book about the brain and then to your interview about your book on HeartWise Ministries [where] I found out about [Come And Reason Ministries]. I’m now devouring the webcasts of your Bible studies. I have been so greatly blessed and I thank God so much for your courage to speak the Truth in love no matter what. Listening to you contrast the two opposing systems (laws) and digging deep to unearth the hidden treasures in the Bible makes me so incredibly happy and I feel very blessed to be part of your Bible Study Group although I live far away. I am just so excited that there is a group of people that is spreading the Truth about the character of God and it saddens me how few realize what our Father in Heaven is really like.

Kessy B., Australia

 

Testimony 71

When I was 9 years old, I remember setting at our devotional table with a hunger and thirst for God that wanted more, deeper, BETTER. I can remember literally crying and pounding on the table, “I know these teachers didn’t mean to give us error. They taught what THEY had been TAUGHT, but didn’t ANYBODY READ THE BOOK?!?!?” It mattered to me then. It mattered to me as a teenager. It matters now as I teach bible classes. It didn’t have to be so hard as I watched so many give up and lay God’s great plan and gift of salvation aside as being “impossible.” Then, a friend sent me a link to Come And Reason’s website. I grew excited. YES! FINALLY! Then another friend told me to stay away, saying her son had just broken up with a girl because she was involved with Come And Reason and that “Tim Jennings preaches a false gospel.” But, AFTER many years of developing an authentic and, dare I say FUN relationship with Jesus, through the Holy Spirit I see this message has been around a LONG time, since the apostle Paul, Ellen White, Graham Maxwell, Ray Foucher, and yourself (though I admit, you’ve made me back up, rewind and replay the clips, and get out my well-worn Bible on a few things.) I’m so thankful I have found LIGHT during these DARK days. I am not alone.

Vicki DiNitto