Causal Link Between Alzheimer’s Disease and Telomere Shortening

In a newly published study, researchers at Karolinska Institutet show that the shortening of the telomeres – the caps at each end of the chromosomes in our cells – can be linked statistically to the active mechanism responsible for Alzheimer’s disease. However, the effect is small and telomere length cannot yet be used to assess disease risk at an individual level. The results are presented in the journal JAMA Neurology.

Every cell in our body contains our entire genome, packed into the nucleus in the form of 46 chromosomes. Every time a cell divides, the telomeres at the tips of the chromosomes become slightly shorter until they reach a critical length, at which point the cell dies. Just where this critical threshold goes depends on the individual, partly because the telomeres are of different lengths to start with, and partly because in some people the telomeres shorten more on cell division than in others. The shortening process takes place when we age, but previously telomere length was only used as a marker for biological ageing.

For the first time, a group of scientists at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet has shown that telomere length is causally linked to the risk of developing Alzheimer’s disease.

“That there’s some kind of link between telomere length and the risk of Alzheimer’s disease is nothing new in itself, but it was thought that it was down to other underlying commonalities,” says principal investigator Dr Sara Hägg, docent of molecular epidemiology. “In this study we’ve been able to show that the telomeres are involved in the actual active mechanism behind the development of the disease, which is completely new and very interesting.”

The entire genome

To arrive at their results, the researchers used data from studies that identified gene variants linked to telomere length and to Alzheimer’s disease by examining the entire genome. By using a special study design, they were then able to show statistically the presence of a causal link between short telomeres and a higher risk of Alzheimer’s disease. The researchers stress, however, that since the telomere process is so complex, nothing can be said about the degree of an individual person’s risk from the mere measurement of their telomeres.

Image shows telomeres.

“What’s more, the effects are very small,” adds Dr Hägg. “But from a biological perspective, they’re very interesting.”


Funding: The study was financed with grants from various bodies, including the Loo and Hans Österman Foundation, FORTE, the Swedish Research Council, KID-grant from Karolinska Institutet for doctoral education, and the Foundation for Geriatric Diseases at Karolinska Institutet.

Source: Katarina Sternudd – Karolinska Institute
Image Source: The image is credited to Reinhard Stindl and is licensed CC BY-SA 3.0
Original Research: Abstract for “Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization Study” by iqiang Zhan, MD; Ci Song, PhD; Robert Karlsson, PhD; Annika Tillander, PhD; Chandra A. Reynolds, PhD; Nancy L. Pedersen, PhD; and Sara Hägg, PhD in JAMA Neurology. Published online October 2015 doi:10.1001/jamaneurol.2015.1513


Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization Study

This study explores the causal effect of telomere length on Alzheimer disease by applying the mendelian randomization method to summary genome-wide association study data.

Telomeres are sequences of repetitive nucleotides at the end of the chromosomes, which protect them from fusion with neighboring chromosomes.1 Observational studies have found associations between shorter telomeres and Alzheimer disease (AD).2 However, these studies could have residual confounding or reverse causation, making it difficult to draw conclusions on whether telomere length (TL) is causally associated with AD. For the past decades, instrumental variable (IV) analysis has been developed for assessing causality using genetic variants in epidemiological research under the name of mendelian randomization (MR).3 In the present study, we investigated the causal effect of TL on AD by applying the MR method to summary genome-wide association study (GWAS) data from Codd et al4 and from the International Genomics of Alzheimer’s Project Consortium.5

“Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization Study” by iqiang Zhan, MD; Ci Song, PhD; Robert Karlsson, PhD; Annika Tillander, PhD; Chandra A. Reynolds, PhD; Nancy L. Pedersen, PhD; and Sara Hägg, PhD in JAMA Neurology. Published online October 2015 doi:10.1001/jamaneurol.2015.1513

Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes

  • Vitamin D metabolism is conserved between nematodes and mammals
  • Vitamin D prevents the age-dependent accumulation of SDS-insoluble proteins
  • Vitamin D enhances lifespan and protein homeostasis via IRE-1, XBP-1, and SKN-1


Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3) induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

Vit D study 1.JPG

Vitamin D, calcium homeostasis and aging, an ebook


Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance.



Expanding the association between the APOE gene and the risk of Alzheimer’s disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription, an ebook


Alzheimer’s disease (AD) is the most commonly diagnosed form of dementia in the elderly. Predominantly this disease is sporadic in nature with only a small percentage of patients exhibiting a familial trait. Early-onset AD may be explained by single gene defects; however, most AD cases are late onset (> 65 years) and, although there is no known definite cause for this form of the disease, there are several known risk factors. Of these, the epsilon4 allele of the apolipoprotein E (apoE) gene (APOE) is a major risk factor. The epsilon4 allele of APOE is one of three (epsilon2 epsilon3 and epsilon4) common alleles generated by cysteine/arginine substitutions at two polymorphic sites. The possession of the epsilon 4 allele is recognized as the most common identifiable genetic risk factor for late-onset AD across most populations. Unlike the pathogenic mutations in the amyloid precursor or those in the presenilins, APOE epsilon4 alleles increase the risk for AD but do not guarantee disease, even when present in homozygosity. In addition to the cysteine/arginine polymorphisms at the epsilon2/epsilon3/epsilon4 locus, polymorphisms within the proximal promoter of the APOE gene may lead to increased apoE levels by altering transcription of the APOE gene. Here we review the genetic and biochemical evidence supporting the hypothesis that regulation of apoE protein levels may contribute to the risk of AD, distinct from the well known polymorphisms at the epsilon2/epsilon3/epsilon4 locus.

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Environmental Magnetite in the Human Brain

Mineral nanoparticles similar to those that have been associated with Alzheimer’s disease may enter the brain through the inhalation of polluted air.

By Ashley P. Taylor

In more than three dozen postmortem human brains, scientists have detected nanoparticles of magnetite that they suspect came from the environment. The brain produces magnetite particles that are associated with Alzheimer’s disease, but these endogenous particles are angular in shape, whereas the newly discovered compounds are spherical. Their shape and other properties suggest that the nanoparticles were generated during high-temperature processes like combustion.

The results, published yesterday (September 5) in PNAS, suggests that inhaled magnetite, which is known to be a ubiquitous air pollutant, can make its way to the brain. Barbara Maher, an environmental scientist at the University of Lancaster, and her coauthors now speculate that this environmental magnetite could pose a health risk.

“This is the first report of iron oxide particles in brain tissue that may have come from an industrial source. As such, this opens up questions about potential neurotoxic effects from industrial pollutants that had not been previously considered,” University of Florida’s Jon Dobson, who researches the potential neurodegenerative role of biologically produced magnetic compounds and was not involved in the study, told The Scientist in an email.

In 1992, researchers discovered angular particles of magnetite in the human brain. Sixteen years later, a comparison of healthy and Alzheimer’s brains revealed that higher levels of magnetite correlated with the incidence of disease. Most recently, scientists studying rat neuronal cell cultures found that magnetite and amyloid-β peptides seemed to stabilize each other; the two particles together were more harmful to neurons in culture than amyloid-β peptides alone.

Maher had been studying the airborne particulate matter, including magnetite, along roadsides, and decided to examine whether that magnetite might enter the brain, where it could potentially have similar toxic effects. She and her colleagues examined the quantity and structure of the magnetite within frontal cortex samples of 37 human brains, which came from the Manchester Brain Bank in the U.K. and from people who had died in fatal accidents in Mexico City between 2004 and 2008.

Using high-resolution transmission electron microscopy, the researchers searched the brain slices. They identified endogenous, angular magnetite particles, which ranged in diameter from 50 to 150 nanometers, as well as spherical particles that ranged from less than 5 nanometers to more than 100 nanometers. The researchers believed these spherical compounds came from particulate matter in the air, Maher said.

Both in shape and in texture, these round magnetite particles resembled magnetite particles from roadside particulate matter, “and some of the particles have some very distinctive surface textures,” Maher said. Moreover, the magnetite particles “co-occur with other rather exotic metals, [which] are not metals that you would expect normally to find in the human brain,” she added. The researchers hypothesize that magnetite particles from the air are inhaled and enter the brain via the olfactory bulb, a neuronal gateway to the brain that does not have the same blood-brain barrier protection that other brain regions do, Maher said.

Dobson noted that a causal link between magnetite particles of any type and neurodegeneration has not been established. However “mechanisms proposed for a potential role in neurodegeneration would be the pretty much the same for both types of particles,” he added.

Although researchers do not know if environmentally derived magnetite has the same effects as endogenous magnetite on neuron health, “it would be foolish to ignore the possibility that it could be creating an additional health hazard for humans,” Maher said.

The study “gives an explanation for the high abundance of magnetite in the brain and, in turn, points towards its connection with Alzheimer’s,” Jordi Soriano, a University of Barcelona biophysicist who has studied magnetite’s effects on neurons in cell culture and was not involved the present study, told The Scientist in an email.

He noted, however, that the researchers did not sample any brains from people who had lived in nonurban areas, which would be necessary “to prove the connection between pollution and magnetic nanoparticles accumulation and structure.” This type of epidemiological study correlating likely magnetite exposure and neurodegenerative disease is one area for future research, Maher said.

B. Maher et al., “Magnetite pollution nanoparticles in the human brain,” PNAS,doi:10.1073/pnas.1605941113, 2016.

A platform for health consumers to stop cancer early and collaborate with health care teams

indi final.JPG

Short Summary

  • I am Connie Dello Buono, health author and blogger at ( soon )
    Since 2000, I have cared for seniors with cancer, Alzheimer’s and Parkinsons.
    My passion is help reduce chronic care costs, health education and personalize medicine using telemedicine.
  • This campaign will address cancer health issues, identifying root causes early, connecting with doctors real time, access to telemedicine and tele-clinics, matching providers using mobile application and a health application that will hep reduce chronic care costs.
  • As contributors, you will help achieve our goal of reducing chronic care costs thru telemedicine, personalize medicine and a health mobile application serving all population groups.

Motherhealth Inc

Management Team

  • Maddalena Adorno PhD, CTO. She is a professor at Stanford University Institute for Stem Cells and Regenerative Medicine
  • Connie Dello Buono, CEO. She is a health author and completed her B.S in Mathematics with minor in Chemistry at Adamson University, Manila Philippines

What We Need & What You Get

  • $5000 of the funds will go to the mobile application developers and marketers.
  • Your unique perks will be a lifetime discount, 20%, in the many health apps that will come out of this first phase of the product.

The Impact

  • or Motherhealth aims to help health consumers navigate in their health issues and collaborations with health care professionals by providing a platform for them to order their genetic and lab tests, join in health care forums, learn about health care issues and prevention, set up appointment with others and health care teams, find and post health care jobs, video chats with doctors and a health concierge provided online and in the future, via a mobile application.
  • Globally, we can now correlate health data and provide valuable insights to all, scientists and the population.
  • Since 2000, I have been educating the public on health, wrote an ebook on women’s health, was pharmacy tech instructor, a senior care administrator and care provider, and quality assurance in many biotech and medical device companies in the USA.

Alzheimer’s Disease Risk Factor Formula

ad genes.JPGAlzheimer’s Risk Factor, formula by Connie Dello Buono , ©12Sept2016

Assumption: Female, over 60yrs of age, on western diet, lives in Northern hemisphere, have families with cancer, diabetes and dementia, prone to allergies (lack zinc), digestive disorders, high dairy and sugar consumption (low magnesium and calcium,iron) and had used some medications in the past

Alzheimer’s Disease (AD) Factor = Blood sugar (0.2) + Blood Pressure (0.2) + Hard cheese and pork consumption (0.1) + Exercise and sun exposure (0.1) + number of medications (0.1) + stress level and brain concussions (0.1) + exposure to copper,fungus,molds,toxins (0.1) + genes (0.1)

  • AD Factor =1.0 (High)
  • AD Factor = <0.8 (Medium)
  • AD Factor = <0.5 (Low)

Please email your entries to to create a database and get health data insights about Alzheimer’s disease. The link below contains the table in Microsoft Word. This data will also be used to track cancer, diabetes, lung disease, depression, mental health and heart disease.

Modified Alzheimer’s disease risk factor

Male = 0.05
Female =0.1
Age > 55yrs=0.1
< 55yrs = 0.05
Blood sugar
Normal/low =0

High = 0.1
Med =0.05

Blood Pressure
High = 0.1
Med =0.05
Exposure to copper,fungus,molds,toxins, smoking,alcohol,narcotics, aluminum, air pollution, medications > 5
(H,M,L)  0.2 = H,M = 0.1
Metabolic and diet:
Diabetes 0.1
Exercise and sun exposure, 3x per week = 0
No exercise = 0.1
0.1 (combo of these genes) –
Aβ42 ;  presenilin 1 & 2 ; APP ;  CASS4  CELF1  FERMT2
EPHA1, and CD2AP
Weak immune and metabolic system:
Infection and allergy 0.1


Stress level and brain concussions (H,M,L)
H = 0.1




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