causes of Alzheimers

Three d

My wife has recently died of Alzheimers. Over the past 3 years I have read a ton of information on Alzheimers and time and time again I have read that if you have certain things like high blood pressure or diabetes or you don't exercise or you smoke or drink or you don't socialize or you don't have an extended education contribute to getting Alzheimers. My wife had none of these. so I'm having difficulty understanding why this horrible disease took the life of my wife.

Crushed

Its very simple
WE HAVE NO IDEA WHAT CAUSES MOST ALZHEIMER'S

Everything you describe is only statistically associated with Alzheimer's
Makes for QUACK heaven 
 
My wife was a physician , never smoked or drank and  weighs 120 pounds after gaining weight.  No dementia in her family.  Yet at 58 she could not add simple numbers.

It tears your guts out.

you have my sympathy

Paris20

My mother-in-law’s greatest fear was that she would die of Alzheimer’s Disease, as her mother did at age 62. She died of heart disease when she was in her 80’s. However, her son, my husband, has Alzheimer’s Disease. He was diagnosed in his mid-70s. He drank rarely, stopped smoking 50 years ago, ate a proper diet, and exercised five days a week. Did he get AD through heredity or just bad luck? No one knows.

Jimbob59

I believe heredity plays a big roll in Alzheimer's. My grandmother died at 72 with it, my mother her daughter has it, 3 of moms brothers and sisters died with Alzheimer's. One of her living brothers has it. My 72 year old cousin died last year and two of my 60 something cousins have it now. There may be more in the family their was 11 brothers and sisters and I never here about some of the cousins.

Crushed

Jimbob59 wrote:

I believe heredity plays a big roll in Alzheimer's. My grandmother died at 72 with it, my mother her daughter has it, 3 of moms brothers and sisters died with Alzheimer's. One of her living brothers has it. My 72 year old cousin died last year and two of my 60 something cousins have it now. There may be more in the family their was 11 brothers and sisters and I never here about some of the cousins.

It is well established that Heredity plays a part in some Alzheimer's however
 In the vast majority of cases (more than 99 in 100), Alzheimer’s disease is not inherited.
 https://www.alzheimers.org.uk/about-dementia/risk-factors-and-prevention/is-dementia-hereditary

Clearly being part of a familial Alzheimer's cluster gives the Impression that heredity pays a big part but that is misleading

Larrytherunner

According to what I have read, some researchers are classifying early onset Alzheimers disease and familial Alzheimers disease into one category of Early Onset Familial Alzheimers Disease (EOFAD), possibly because they are both associated with the same genes.

I have to say that Alzheimers UK is giving out misleading information - to say that Alzheimers is not inherited in 99 In 100 cases. Maybe they have good intentions of reducing peoples fears, but APOE4 and a host of other genes associated with Alzheimers are inherited and they are risk factors. When you say that Alzheimers is not inheritable, you imply that these genetic risk factors are not inheritable. You need to explain. Plus EOFAD cases make up 1 to 5 per cent of dementia cases and have strong genetic association.

https://memory.ucsf.edu/genetics/familial-alzheimer-disease

Lane Simonian

There are multiple causes of Alzheimer's disease.  Some risk factors have been better established than others (genetic mutations, high blood pressure, and high blood sugar, for instance).  Other causes currently have less weight behind them, but they may include exposure to air pollutants, heavy metals, and various pesticides and herbicides, pyschological stress, anesthesia (as mentioned above), the ApoE4 gene, Down syndrome, bacterial, fungal, and viral infections, multiple concussions, and traumatic brain injuries.  The reasons why Alzheimer's disease is so common is that so many factors can cause the disease.

Indeed any factor that can damage the brain can potentially cause Alzheimer's disease:

There have been several papers, says Dr Le Guillou, that have found correlations between various infectious organisms and Alzheimer’s. “It could be a bit like the Mississippi river,” says Dr Hardy. “You can start in all sorts of places, but eventually you’re going to end up in New Orleans.” If Alzheimer’s is a general response to all sorts of neurological triggers then it may be that the fungal infections found by Dr Carrasco are simply one of a long list of causes.

The problem with almost all current efforts to treat Alzheimer's disease is that they are focusing only on one single factor that causes the disease, or that they are focusing on secondary triggers such as amyloid, tau, and inflammation.

I don't care if they give me a Nobel prize or not, but the primary cause of Alzheimer's disease is very likely oxidation and nitration.  Every single factor assocated with Alzheimer's disease causes oxidation and nitration, every feature of the disease is due either directly or indirectly to oxidation and nitration, and every treatment that has nearly stablized the disease has not only reduced oxidation and nitration it has partially reversed it.

 

Marta

Oxidation and nitration are common causes of aging, and of cell death in multiple disease states.

Quilting brings calm

I agree with Marta - which is why I personally think dementia ( not early onset) is often a result of outliving our brains’ age limit.  We’ve fixed so many diseases and infections, repaired injuries that formerly caused the average life span to be much less than it is now.  So it’s to be expected that living to an older  age allows the breakdown of our bodies and minds due to old age.

However, yes, I think genetics plays a factor in how long we live and how long everything functions too. 

Lane Simonian

I imagine your comment was meant to be dismissive, Marta, but you have stumbled onto the truth.

Nitric oxide and peroxynitrite in health and disease

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

This one is more specifically for Alzheimer's disease.

The hippocampi – the brain centres for learning and memory – are one of the earliest regions to be sabotaged by Alzheimer’s pathology. Our data revealed that GSH [the antioxidant glutathione] levels plummet in the hippocampi of patients with Alzheimer’s as well as those with MCI. The frontal cortices – brain CEOs responsible for a variety of executive functions – are chronologically affected later in Alzheimer’s. GSH levels mimic this chronology with no changes in the cortices of MCI patients, but significant reduction in those of Alzheimer’s patients. Interestingly, GSH remains unaffected in the cerebellum – a brain region unaffected by Alzheimer’s till late stages. It appears GSH decline is not ubiquitous but rather a region-specific phenomenon that appears to precisely map the progression of Alzheimer’s in our brains.

Marta

I learned this in grad school, if that is what you mean by stumbling.

Lane Simonian

By stumbling onto the truth, I meant the following: oxidation and nitration are often acknowleged to be part of the aging and disease process, but then the idea is that they are so common to both that they are not in any way critical to either.  But they are and that is how you stumbled onto the truth.

Marta

Lane, you are a hoot.

Crushed

I have to say that Alzheimers UK is giving out misleading information - to say that Alzheimers is not inherited in 99 In 100 cases. Maybe they have good intentions of reducing peoples fears, but APOE4 and a host of other genes associated with Alzheimers are inherited and they are risk factors. When you say that Alzheimers is not inheritable, you imply that these genetic risk factors are not inheritable. You need to explain. Plus EOFAD cases make up 1 to 5 per cent of dementia cases and have strong genetic association.

 

You are misusing language
Risk factors are called risk factors since they are not shown to be causative
  APOE ɛ4 is called a risk-factor gene because it increases a person's risk of developing the disease. However, inheriting an APOE ɛ4 allele does not mean that a person will definitely develop Alzheimer's. Some people with an APOE ɛ4 allele never get the disease, and others who develop Alzheimer's do not have any APOE ɛ4 alleles. https://www.nia.nih.gov/health/what-causes-alzheimers-disease

and no you cannot automatically lump ALL early onset with familial Alzheimer's

Some cases of early-onset Alzheimer disease are caused by gene mutations that can be passed from parent to child. This results in what is known as early-onset familial Alzheimer disease (FAD). Researchers have found that this form of the disorder can result from mutations in the APP, PSEN1, or PSEN2 genes 
https://medlineplus.gov/genetics/condition/alzheimer-disease/#causes
  
 
It is unquestionably true that the percentage of Alzheimers that is familial increases with younger onset.  but at age 55 to 65  the description as early onset is social not medical 
  
  There is mounting evidence that only a small fraction of early-onset Alzheimer disease cases (onset <65 years) are explained by known mutations. Even multiplex families with early onset often also have late-onset cases, suggesting that the commonly applied categorization of Alzheimer disease into early- and late-onset forms may not reflect distinct underlying etiology. 
 https://ng.neurology.org/content/6/5/e512

Late-onset vs nonmendelian early-onset Alzheimer disease

 

A distinction without a difference?

Christiane Reitz, Ekaterina Rogaeva, Gary W. Beecham

Neurol Genet Oct 2020, 6 (5) e512; DOI:
 

BlueMax

My DW has early-onset at 61 and genetic testing revealed that she carries one APOE 4 gene.  There are many other factors the care team (who are also AZ research group), identified as potentially contributing, such as high stress she endured through a protracted situation, prescription drugs, several concussions, and alcohol.  That said, they stated that none, including the APOE 4 gene, are the cause of her AZ as they just don't know what exactly triggered it.  

To guide our children they stated that her APOE 4 gene increased her chance of getting AZ, and if caused by that gene, it is almost always early-onset.  Most importantly, should our children also have this gene it does not mean they will also get AZ.  They stated a key difference between the APEO 4 gene connection and familial AZ is the later occurs at a younger age and always occurs in each generation.    

She is now participating in the LEADS study that is researching 5 other genes to see if there is a link between them and early-onset.  Although any findings will not help her, she hopes that more definitive results will help future generations.    

Iris L.

BlueMax wrote:

To guide our children they stated that her APOE 4 gene increased her chance of getting AZ, and if caused by that gene, it is almost always early-onset.  Most importantly, should our children also have this gene it does not mean they will also get AZ.  They stated a key difference between the APEO 4 gene connection and familial AZ is the later occurs at a younger age and always occurs in each generation.    

This is puzzling to me.  I am APOE 4 positive with cognitive impairment nos but I don't have Alzheimer's Disease.  I am 71 years.  A few of my mother's first cousins have or have had late onset AD.  On my father's side none of his relatives had AD, but one of my paternal first cousin's has late onset AD.  My neurologist told me that I don't have AD yet.

Iris

Crushed

The term "risk factor" is routinely used by people who have no idea of the different ways the term is used. 

First a "risk factor" is not a "risk"

Risk is a probabilistic concept that has specific definitions and uncertainty 

Risk factors are  events which may change the risk or our levels of uncertainty
  
The connection between   risk factors evens is often indirect.

e.g. Drunkenness may be an enhanced  risk factor for women in pregnancy.  But it might be a reduced factor for  men  As Shakespeare wrote "it provokes the desire, but it takes away the performance, 

 
In some analysis RISK FACTOR simply refers to statistical association 
 If you have A you have a higher probability of finding B

More sophisticated analysis  requires meaningful probability of causation   in addition to statistical association.   

If you have A you have a higher probability of finding B because we have separate reasons to believe that A causes B

Some belief structures are strong like Gravity   Some are middling , like biological plausibility and double blind studies. 
, and some are weak such as social sciences and observational studies. 
and some are simply ludicrous and political 
 We have tools for evaluating the relative strength of causative beliefs.

These  risk issues are compounded by the routine difficulty of measuring A and B 
e.g. how would we know that an Alzheimer's drug WORKS? 
  
 The final problem is what we call reification   That is the false belief that because we have a measurement output or a definition that the underlying entity EXISTS as a real thing.
Does early onset Alzheimer's exist as a real entity or is it merely a definition
 We know familial Alzheimers exists.  Younger people with non familial Alzheimer's may just be the tail end of a statistical distribution.

  

KatieKat1

In my husband's case, who passed away this past August, it seems that his dad and brother had this dementia at different levels.  His brother had Dementia and then Parkinson Disease.  His dad had Alzheimer but my husband had a worse form of it.

 

I think but not positive that my husband was affected by the Chemotherapy he received for bladder cancer many years ago.  I have heard of Chemo brain and it was effective in getting rid of the cancer he had that never came back but my thoughts is that it did possibly affect his brain and from what I have read on various medical web sites this does happen, but not experts agree on this.  Maybe it is the type of Chemo they use.  In my husband's case it was Cisplatin.  DH may have also been predispositioned for Alzheimer taking into account of his dad's and brother's situation but I often wonder if the chemotherapy contributed.

Saying all of this, I am thankful that since he was treated for the cancer with this chemotherapy and did not pass on from cancer, we were able to enjoy life together for another 12 years after treatment and that is a blessing in itself.