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   Oct 22

Why some with the ‘Alzheimer’s gene’ do NOT develop the disease

The ApoE4 gene increases the risk of Alzheimer’s, but has also been detected in people who never develop neurodegenerative disease

Boston University School of Medicine researchers have a theory as to why in a paper published today

The study suggests chronic inflammation and ApoE4 together increase risk

Preventing inflammation, they believe, could reduce the rate of infections, which is climbing as the population ages

Chronic low-grade inflammation could explain why some people with the ‘Alzheimer’s gene’ develop the disease and others don’t.

For years, researchers have been baffled by the ApoE4 gene, which is linked to 50 percent of Alzheimer’s cases, but has also been detected in people who never develop neurodegenerative disease.

A study published today by neuroscientists at Boston University School of Medicine suggest a theory: the gene may only increase one’s risk if it is aggravated by chronic low-grade inflammation, which could come from countless things including high blood pressure, diabetes, pneumonia, and urinary tract infections.

Preventing inflammation, lead author Wendy Qiu says, could reduce the rate of diagnoses by ‘a dramatic number’.

She says the findings offer yet another reason to treat inflammation as a critical concern for our health, not least to prevent heart disease, the biggest killer in the US and globally.

‘I have seen so many patients seem fine but then after pneumonia or after a surgery their cognition deteriorates. Not all of them, but some of them,’ corresponding author Dr Qiu, MD, PhD, said.

‘I feel very excited that this study has opened up a new clinical research perspective [to explain why].’

Dr Qiu explains that chronic low-grade inflammation ‘is very easy to measure, and it’s so common,’ and APOE4 is easy to detect, too.

‘We should measure it every year. If a patient has pneumonia and they are an ApoE carrier, we should follow them every three months.

‘If we rigorously treat that chronic systemic inflammation in ApoE4 carriers, we could prevent a dramatic number of Alzheimer’s dementia cases.’

Chronic low-grade inflammation is when the body persistently launches defensive responses to threats – but the threat isn’t there.

It dispatches an army of white blood cells to deal with the attack, but they have nothing to do so they end up bumbling around aimlessly, attacking tissues and cells as they go to wile away the time.

The body gets used to this experience, so low-grade inflammation rarely triggers actual symptoms that could alert a doctor to it.

It can be detected, though, by screening for CRP (C-reactive protein levels) in a blood test, but this is only really done during tests for more immediate threats, like lupus or arthritis, so many are never aware of their condition.

The inflammation-dementia connection is not exactly new, but until now, it hasn’t been clear how it may increase the risk, just simply that most Alzheimer’s patients seem to have a lot of inflammation.

The new study, published today in JAMA Network Open, was the first to compare inflammation to specific types of the ApoE gene (2, 3, and 4) over a years-long period. Previously, studies had measured their inflammation levels once.

This one showed a clear distinction.

They looked at data on 3,000 people from the Framingham Heart Study, comparing their genes and CRP levels.

Once inflammation was eliminated, the ApoE4 carriers had no higher risk of developing AD than their ApoE2- and ApoE3-carrying peers.

Qiu, associate professor of psychiatry and pharmacology & experimental therapeutics at BUSM, believes screening for and treating chronic inflammation with diet and exercise and medication – especially in ApoE4 carriers – may well be the thing that determines whether a person gets the disease or not.

It could be a groundbreaking discovery if so. Alzheimer’s disease is such a mystery that cannot be treated or cured, and technically it cannot even be definitively diagnosed until after death in an autopsy.

The race to find a cure or treatment is fierce, both from a public health perspective and a business one. Pharmaceutical companies around the world are scrambling to become the first to thwart Alzheimer’s – and win a goldmine.

Despite some significant progress, trial after trial comes up short.

Dr Qiu believes that that may be down to the fact that most trials, which have been trying to target inflammation, have not broken it up into genotypes.


While researchers put Dr Qiu’s findings into action, the rate of people suffering from the disease climbs – as does inflammation.

With poorer diets, more inactivity, more pollution, more stress and more sleeplessness, obesity and diabetes have reached epidemic levels globally.

It’s increasingly clear that genetics may play a role when it comes to some inflammatory diseases like obesity and diabetes.

However, there are effective lifestyle changes that will lower inflammation for most.

All of this has been known for years, but – as is clear from the rising numbers of inactive people with fatty diets – no public health campaigns have been persuasive enough to turn the tide.

The threat of losing one’s mind to Alzheimer’s may well be the most persuasive argument yet.

Source: Daily Mail

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