NEUROGENESIS: YES OR NO?
One of the earth-shaking discoveries made by modern neuroscience is that human brains remain plastic and changeable throughout life. One of the key pieces of evidence in support of brain plasticity is neurogenesis. Only within the past 20 years has it become accepted wisdom that the human brain generates new brain cells throughout our lifetime.
But now, a recent study from a team of researchers at the University of California San Francisco has raised some eyebrows. They challenge the idea of human adult neurogenesis. They say they found no evidence to support the birth of new neurons in human adult brains.
Their claims have been met with great skepticism and have sparked a healthy debate. Nevertheless, they are sticking with their story. They say that “repeated and varied experiments convinced us our conclusions were correct: New brain cells don’t grow (or are extremely rare) in the adult human hippocampus, a region important for learning and memory.”
This is, of course, just one study. There are plenty of others that seem to confirm the presence of neurogenesis. But, this how science works! We can’t dismiss evidence just because it contradicts cherished beliefs. We need to assume the classic, “Hum! That’s interesting” stance and keep an open mind. Then, we look for more data that either supports our current beliefs or supports the alternative view.
One study, that appeared soon after the UCSF study, for example, found evidence for adult neurogenesis. And, their discussion raised a number of interesting points that shed light on the difficulty of identifying whether new brain cells are being generated.
First, different researchers apparently use different techniques to look for neurogenesis. One technique is to look for proteins that are proxies for new neurons. If the protein is present, researchers make the assumption that new brain cells are present. They don’t actually see the new neurons. And, researchers look for new brain cells in different places. The team that found no neurogenesis apparently searched in a thin slice of the hippocampus. The group that found neurogenesis looked at the entire hippocampus.
Second, neurogenesis is a multi-stage process. Things can go wrong at any one of the developmental stages. Stem cells might produce plenty of neural progenitors and immature neurons that die before becoming mature neurons. How do we define neurogenesis? Is it the production of new brain cells whether they survive or not? Or, are we talking about new brain cells that survive and become active? I’d vote for the surviving neuron definition.
Finally, adult hippocampal neurogenesis (assuming it exists) appears to decline in some older people, but not all. The decline may have nothing to do with the ability of stem cells to pump out potential neurons. The decline may be due to unfavorable conditions, in some older brains, that prevent new neurons from completing their arduous multi-stage developmental journey.
An older brain that is compromised by conditions that cause cognitive decline it may not have the resources needed to support baby brain cells. Conversely, an older brain that is still strong and resilient should do a better job of nurturing health new brain cells.
So, we keep learning.
Two quick final points! First, there is more to brain plasticity than neurogenesis. Even if it turns out that old brains are not refreshed with a steady supply of baby neurons, old brain cells still grow, change, adapt, atrophy and die. Old brain cells, neurons, and glial cells, remain plastic. Second, the healthier we keep our brains, the more likely they are to support positive plastic changes. If we neglect the health of our brains we are more vulnerable to disorders that may well interrupt the ability of the brain to repair and renew itself.
1. Sorrels, S., Alvarez-Buylla A. and Paredes M. Adult human brains don’t grow new neurons in hippocampus, contrary to prevailing view. http://theconversation.com/adult-human-brains-dont-grow-new-neurons-in-hippocampus-contrary-to-prevailing-view-93123. March 12, 2018
2. Boldrini, Maura et al. (2018) Human Hippocampal Neurogenesis Persists throughout Aging. Cell Press. April 5. https://doi.org/10.1016/j.stem.2018.03.015
A NEW BIOLOGICAL DEFINITION OF ALZHEIMER’S DISEASE
The Alzheimer’s Association and the National Institute on Aging have gotten together to update their 2011 recommendations on how to diagnose Alzheimer’s. Rather than use a “syndromal” definition (i.e. signs and symptoms) like the 2011 version, the updated 2018 definition is biological, based on biomarkers.
The bottom line is that the working group has decided that Alzheimer’s syndrome is defined by the presence of abnormal amyloid and tau. This biological approach enables researchers to handle situations in which a person without symptoms is found to have high levels of amyloid and tau.
This discrepancy could lead some to the conclusion that amyloid and tau have no tight link with Alzheimer’s. But, the workgroup goes the other way. If amyloid and tau are present, even though you show no signs of cognitive decline, you have Alzheimer’s. This approach also accommodates the need to make early, pre-symptomatic diagnoses of Alzheimer’s. You may not be showing any symptoms of Alzheimer’s – YET – but if you have abnormal levels of amyloid and tau, you’ve got it.
But, they might be wrong. “Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia.” So, once again, we may ultimately find that amyloid and tau do not cause Alzheimer’s, but if they are present, we will call it Alzheimer’s.
An extended definition adds neurodegenerative/neuronal injury to the equation. This enables the workgroup to propose different stages of a disease continuum based on which biomarkers are present.
If amyloid alone is detected (A+), it is called Alzheimer’s pathologic change, an early stage of the Alzheimer’s continuum. When tau is added to the equation, (A+T+) we can safely say it is Alzheimer’s. Finally, A + T+ along with neurodegenerative/neuronal injury (A+T+(N)+) strengthens the diagnosis.
But, according to the workgroup, neurodegenerative/neuronal injury is not a necessary component of the definition. The N is put in parentheses (N) because it a “concomitant suspected non-Alzheimer’s pathological change.” If (N) is present without A or T, you have some other kind of dementia, not Alzheimer’s. Got it?
Their basic hypothesis is “a modified amyloid cascade hypothesis.” The most likely progression of Alzheimer’s starts with the presence of abnormal amyloid, which leads to the presence of tau, which in turn causes neurodegenerative damage, which in turn leads to cognitive decline. They chart this relationship as follows:
A à T à (N) à (C)
They concede that other types of progression could exist. Tau might appear before amyloid, for example. Or, some as yet unknown pathological process could induce A, T and (N), which then combine to cause cognitive decline. The authors even acknowledge that amyloid and tau might be “epiphenomena that are not in the causal pathway of (N) or (C).” This seems to be the single mention of alternatives to the amyloid hypothesis.
The workgroup stresses that this is not a definition that should be used in a clinical setting. It is merely for research purposes. “It is called a ‘research framework’ because it needs to be thoroughly examined and modified if needed before being adopted into general clinical practice.”
So, I hope that clarifies things for you.
SLEEP AND AMYLOID
Speaking of amyloid, a recent NIH study found that just one night of sleep deprivation elevated levels of beta-amyloid in important regions of the brain.[i] Beta-amyloid, as you know, is considered a biomarker for Alzheimer’s syndrome. Metabolic waste material, like beta-amyloid, is normally flushed out of the brain during deep sleep. So, failure to get a good night’s sleep causes the accumulation of harmful waste material in your brain.
BS (bad sleep) à A à T à (N) à (C)
So, one way to minimize the risk of initiating the amyloid cascade is to improve our sleep habits.
POLLUTION & AMYLOID
Researchers from the University of Montana studied autopsies of people who had lived in Mexico City, one of the worlds most polluted urban areas. They found heightened levels of beta amyloid and hyperphosphorylated tau in the brains of “young urbanites with lifetime exposures to fine-particulate-matter pollution.” The pollution seems to have caused and accelerated the progression of Alzheimer’s syndrome in these exposed people.
The authors conclude that “ambient air pollution is a key modifiable risk for millions of people across the globe, including millions of Americans who are exposed to harmful particulate pollution levels.”
P (pollution) à A à T à (N) à (C)
In other words, exposure to fine particulate matter pollution is one way that the Alzheimer’s disease cascade gets started. Get rid of pollution and we will take away another risk factor for Alzheimer’s
THERE’S NO MONEY IN BEETS!
This drives me crazy. Here is a typical lead paragraph from research institutes.
“A compound in beets that gives the vegetable its distinctive red color could help slow the accumulation of mis-folded proteins in the brain, a process associated with Alzheimer's disease. Scientists say this could lead to the development of drugs that could alleviate some of the long-term effects of the disease, the world's leading cause of dementia.”
My first reaction to this news is. “Hey! Terrific. Let’s eat more beets.” Or, “Let’s figure out what other vegetables have the same kind of compound and eat more of them.”
The first reaction of the science community seems to be, “Wowee Zowee!! Maybe we can develop a drug that mimics the effect of beets.”
Now, you may ask - as do I - why do we need a drug if we already have beets? The answer is obvious. There’s no money in beets! Who is going to fund research projects about eating beets? Who is going to make a gazillion dollars selling beets?
No one! That’s who.
Too many researchers seem bored by the prospect of preventing disease and promoting health. They see their path to fame and fortune in the development of drugs that (possibly, maybe) alleviate symptoms once we have gotten sick. Is it too cynical of me to suggest that this amounts to a desire to promote illness?
[i] NIH/National Institute on Alcohol Abuse and Alcoholism. "Lack of sleep may be linked to risk factor for Alzheimer's disease: Preliminary study shows increased levels of beta-amyloid." ScienceDaily. ScienceDaily, 13 April 2018. <www.sciencedaily.com/releases/2018/04/180413155301.htm>