People With Alzheimer's May Have Their Father's To Thank- The New Scientist

1998From: New Scientist People With Alzheimer's May Have Their Fathers To Thank
CHILDREN born to older fathers have a higher risk of eventually developing Alzheimer's disease, according to a new retrospective study.
Older mothers are more likely to give birth to babies with Down's syndrome, and people with Down's develop Alzheimer's disease earlier and more often than others. Intrigued by the association between these diseases, Lars Bertram of the Technical University of Munich and his colleagues wondered if parental age also plays a more direct role in Alzheimer's.
The researchers studied 206 patients with Alzheimer's disease. Susceptibility to the disease is associated with certain major genes, so their first step was to try to establish each person's inherited risk. To do this they found out the incidence of Alzheimer's in each patient's family.
Then they looked at the groups of patients at each extreme-comparing those least likely to have the disease genes with those most likely to have them-hoping to find an extra risk factor among the first group to explain why they had Alzheimer's.
Those patients who were least likely to have inherited a major disease gene had fathers who were significantly older than fathers of the second group and fathers of people of the same age who did not have Alzheimer's, the researchers report in the current issue of the journal Neurogenetics (vol 1, p 277).
Fathers of this low-probability group had been on average 35á7 years old when their child was born, whereas the fathers of patients who were most likely to have a major disease gene had only been 31á3 years old at the birth of their child.
As people age, researchers suspect, damage builds up in their DNA and gets passed on to the child. "There's an accumulation of environmental factors which somehow alter the genome of the father," says Bertram.
"Their finding is extremely interesting,"says Simon Lovestone, an Alzheimer's disease specialist at the Institute of Psychiatry in London.
Author: Alison Motluk
NEW SCIENTIST issue 19th September 1998



International Psychogeriatrics Copyright © 2006 Cambridge University Press-->
Copyright © International Psychogeriatric Association 2007
doi:10.1017/S1041610207006242
Published online by Cambridge University Press 04Oct2007




Guest Editorial
Elderly persons with elderly fathers – do they face additional risks?
KAREN RITCHIE a1a1 French National Institute of Medical Research (INSERM), Research Unit U888 “Nervous System Pathologies,” La Colombière Hospital, Montpellier, France Email: Ritchie@montp.inserm.fr


George Bartzokis, M.D. explains the reason for the increase in Alzheimer's in offspring of older fathers:



I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth."The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations. The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."



George Bartzokis,M.D. Visiting ProfessorLaboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine 635 Charles Young Drive South, Suite 225Los Angeles, CA 90095-7332

This article is so true

Rather than an infertility crisis, what we have is a society that's allowed technology to displace biology in the reproductive process, in effect dehumanizing the most human of events. At the very least, this means stress replaces spontaneity as women become tied to thermometers—constantly checking to see when they're ovulating—while men stand by waiting to give command performances. At the most, it involves women and men subjecting themselves to invasive procedures with high price tags. Whatever happened to love and romance and the idea of letting nature take its course? Instead, we seem to have embraced the idea that science, not sex, provides the best chance for producing biological children. Technicians have stolen human reproduction. And there are some 300 fertility clinics—with annual revenues of $2 billion—to prove it.

Don't Wait Have Your Babies Older Fathers Bring More Genetic Mistakes in the Sperm to their Babies

Fisch, who authored The Male Biological Clock, believes "the sooner, the better" when it comes to having children -- for both men and women.


"Men thought they were getting off scot free, and they weren't. The birth defects caused by male aging are significant conditions that can cause a burden to families and society," says Ethylin Wang Jabs, professor of pediatric genetics at Johns Hopkins University and leader of a study showing the link between aging paternity and certain facial deformities in offspring. "We now know that men and women alike could be increasing the risk of infertility or birth defects by waiting too long to have children." In other words, by looking for perfection in your life before you conceive, there's a very real chance you'll have less perfect kids."
Studies worldwide have found that with each passing decade of their lives and with each insult they inflict on their bodies, men's fertility decreases, while genetic risk to offspring slowly mounts. The range of findings is staggering: Several studies have shown that the older the man, the more fragmented the DNA in his ejaculated sperm, resulting in greater risk for infertility, miscarriage or birth defects. Investigations out of Israel, Europe, and the United States have shown that non-verbal (performance) intelligence may decline exclusively due to greater paternal age; that up to a third of all cases of schizophrenia are linked to increasing paternal age; and that men 40 and older are nearly six times more likely to have offspring with autism than men under age 30. Other research shows that the risk of breast and prostate cancer in offspring increases with paternal age.
Fisch has found that when both parents are over 35, paternal aging may be responsible for as many as half of all cases of Down syndrome, formerly thought to be inherited from the mother. And recent studies show that half a dozen or more rare but serious birth defects appear to be inherited exclusively from the father, including Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome (all characterized by facial abnormalities and the premature fusion of skull bones) as well as achondroplasia (the most common form of dwarfism).

Worrisome large increases in paternal age in last 25 or so years

Genetic quality of sperm
Although increasing maternal age has long been known to be associated with increased
incidence of birth defects, the age of the male as been seen as irrelevant. New data show
what we should have suspected all along: the age of the male does matter and the genetic
quality of sperm does decline with age. Specifically, a 2004 study by Malaspina et al.,
found that older men are at higher risk of fathering a child with schizophrenia. In fact
men older than forty were more than twice as likely to have a child with schizophrenia as
men in their twenties. A 2003 study (Fisch et al.) found a similar influence of paternal
age on the risk of having a child with Down Syndrome. Paternal age was a factor in half
the cases of Down Syndrome when the maternal age was over 35. And a 2002 study by
Rochebrochard and Thonneau of the rate of miscarriages found similar increased risks
with rising paternal age when maternal age was older than 35. These and other studies
clearly show that when the mother and father are both over the age of 35 years, there is a
markedly increased risk of both genetic abnormalities and miscarriage. The father’s
contribution to these events is increased with increasing age, similar to women. As noted
above, these facts are worrisome in light of the large increases in maternal and paternal
age over the past 25 years.

Prevention of Neurodevelopmental Disorders - Lower Paternal Age SPERM NOT EGGS MUTATE SPERM STEM CELLS DIVIDE EVERY 16 DAYS

Guys have all your children before your 35th birthday to prevent autism, schizophrenia, diabetes, MS, cancers, autoimmune disorders, etc. Best to father babies before 33. The health of the placenta is affected by the sperm DNA. This is not what you've been taught, I know.


Neurodevelopmental Disorders
in proportion to the demographics of
paternal childbearing age. Furthermore, this risk has implications for public health and for the primary prevention of these disorders.


Mutations May Occur in Any One of a Number of
Genes Involved in Neurodevelopment. Thousands of
genes are estimated to play a role in neurodevelopment;
therefore, it is possible that mutations in many genes could cause autism etc.



New Mutations and Human Genetic
Disease
Association With Paternal Age. The major source of
new mutations in human populations is from advancing
paternal age (see Crow 1999). Weinberg (1912) had suggested
that aging parental germ cells may be prone to
mutation after observing that achondroplasia was more
common in last-born siblings. In 1955, Penrose demonstrated
that later paternal age, but not maternal age, was
predictive of de novo mutations. He proposed that mutations
arose by DNA copy errors that accumulate over the
many replication cycles that occur in the male germ line.
Spermatogonial cells replicate every 16 days, approximating
200 divisions by age 20, and 660 by age 40 (see
Drake et al. 1998). By contrast, oocytes undergo only 24
cell divisions, of which all but the last occur before a
woman's birth. In addition, as men age, mutations may
increase because spermatogenesis occurs in the presence
of declining testosterone, lower levels of DNA proofreading
and repair enzymes (Tarin et al. 1998), and reduced
antioxidant enzyme activity, along with the limitations in
vascular supply and reduced cellular efficiency that
accompany aging in other tissues. New genetic diseases
arising from mutations are likely to minimally affect 1 of
every 200 offspring of men older than 40 years (Friedman
1981).
Although