Home » Alzheimer’s, the disease was born 18 years earlier: the eight signals of the countdown

Alzheimer’s, the disease was born 18 years earlier: the eight signals of the countdown

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Alzheimer’s, the disease was born 18 years earlier: the eight signals of the countdown

It’s like a map, within which our brain begins to lose its bearings and lose pieces. Alzheimer’s arrives like this, displacing us year after year. The fact is that the signs of its arrival can appear much earlier, 18 years to be precise according to Chinese researchers who analyzed the phenomenon from the point of view of its occurrence over time, a team led by scientists from Innovation Center for Neurological Disorders – Department of Neurology of Xuanwu Hospital – who collaborated closely with colleagues from different institutes. Thus it was discovered how and when Alzheimer’s can knock on our door: the “how” is given by a series of eight precise signals that appear within the 18 years preceding the onset of the disease.

Alzheimer’s also affects young people

Twenty years before (old age) it appears in our lives, but Alzheimer’s can arrive even when we are very young. The Chinese study published on The New England Journal of Medicine was carried out in collaboration with various institutes, including the Alzheimer’s Disease Center Beijing Institute for Brain Disorders; Anding Hospital and the Department of Psychiatry of Zhejiang Provincial People’s Hospital. And it has ascertained that the variation in the concentration of certain proteins (amyloid beta plaques and tau protein tangles) and the alterations in the brain tissue appear in sequence and at defined stages, until resulting in the pathological condition. It should be remembered that the accumulation of beta amyloid, although considered among the main signs associated with Alzheimer’s, is not present in all affected people.
The clearly anticipated onset of the biological signatures of dementia was known for the hereditary forms of the pathology, which can surprise even at a very early age (the case of a boy suffering from Alzheimer’s already aged 19 should be remembered) but, thanks to new research , the temporal progression of Alzheimer’s biomarkers has also been observed in its sporadic form, which is the most widespread.

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What it is and how many people suffer from it

What is Alzheimer’s disease? In summary, it is the most common form of dementia: a neurodegenerative disease that progressively kills nerve cells, especially those in the areas of the brain that regulate learning and memory processes. The main symptom? Short-term memory loss. If you looked into the brain of a person with Alzheimer’s, you would see suffering neurons surrounded by skeins of a harmful protein, beta-amyloid, surrounded by inflammatory cells that also become dangerous. The brain is damaged at different levels: in addition to the degeneration of nerve cells, there is damage to blood vessels and a state of persistent brain inflammation.

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Alzheimer’s patients around the world

According to the data of the WHO (World Health Organization) There are over 55 million cases of dementia in the world and it is estimated that, due to the progressive increase in the average age of the population, this number will grow, reaching 78 million by 2030. Of all cases, 60 -80% is represented by Alzheimer’s disease. In Italy, according to estimates provided byDementia Observatory of the Istituto Superiore di Sanità, approximately 1.2 million people suffer from dementia, of which 50-60% (600 thousand people) are Alzheimer’s patients and approximately 900,000 show a minor neurocognitive disorder (Mild cognitive impairment) which could convert to full-blown Alzheimer’s. Furthermore, there are approximately 3 million people directly or indirectly involved (relatives, healthcare assistants, doctors).

Some proteins discovered that can predict dementia up to 10 years earlier by Valentina Arcovio 12 February 2024

The Chinese study

Coming to the Chinese study, the researchers coordinated by professor Jianping Jiaconducted a multicenter case-control investigation with thousands of participants, all involved in the study China Cognition and Aging Study (COAST) performed between January 2000 and December 2020. What does it consist of? Over those 20 years, a portion of the volunteers underwent a series of regular tests (every two or three years), including cerebrospinal fluid (CSF) tests, brain scans and evaluation of cognitive function through standardized tests similar to the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Participants were both middle-aged and older men and women (mean age 61 years, 50.6% male) who all had normal cognitive status at baseline. The researchers compared and matched the cases of 648 individuals who maintained healthy cognition (control group) with 648 people who, during the follow-up period lasting exactly 19.9 years, became ill with Alzheimer’s.

The eight signs that announce the disease over time

This procedure allowed the results of tests conducted at regular intervals to be analyzed and matched, and made it possible to determine when and how biomarkers of neurodegeneration manifested themselves, leading up to the onset of cognitive decline and the diagnosis of dementia. Here are the signs that tell us that Alzheimer’s is attacking our brain.

1 – The earliest signal to emerge was an increase in the concentration of the beta-amyloid 42 protein in the cerebrospinal (or cerebrospinal) fluid, already detectable 18 years before the diagnosis of Alzheimer’s.

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2 – 14 years after diagnosis, a difference was detected in the ratio between beta-amyloid 42 and beta-amyoid 40, essentially two forms of “sticky” proteins, whose accumulation in the nervous system is associated with neurodegeneration.

3 – At 11 years of age, the research team observed an increase in phosphorylated tau 181 protein in the Alzheimer’s group.

4 – At 10 years it was the increase in tau as a whole that emerged as an anomaly.

5 – At 9 years old, the first signs of neuronal damage were detected, caused by the presence of the neurofilament light chain (NfL) in the cerebrospinal fluid, which particularly affects the axons.

6 – At 8 years of age, magnetic resonance imaging showed atrophy of the hippocampus, a part of the brain involved in cognition, in the Alzheimer’s group.

7 – 6 years after diagnosis, cognitive decline was evident through standardized tests to evaluate dementia.

8 – In addition to this progression, Professor Jia and colleagues found that in the Alzheimer’s group there was a greater probability (37.2% versus 20.4% in the control group) of being carriers of a genetic variant called APOE4. The data confirms the association, which has already come to light in the past, between this variant of the gene involved in the metabolism and transport of lipids in the brain and the most widespread form of dementia in the world.

Dementia before the age of 65, 15 risk factors identified by Mara Magistroni 12 January 2024

Rossini: “The study only provides confirmations”

He defines the Chinese research as “impressive for the number of subjects recruited and the time period over which they were followed”. But, immediately afterwards, Professor Paolo Maria Rossiniresponsible of Department of Neurological and Rehabilitation Sciences of the Irccs San Raffaele in Romeis quick to point out: “In reality, the conclusions of the study confirm many information known for some time, namely that the accumulation of a matobolite of beta-amyloid, which is not soluble and tends to form fragments which then deposit in plaques, occurs first between 18 and 14 years before the onset of symptoms. It also confirms the fact that the presence of metabolite of the tau protein, which then leads to the formation of neurofibrillary tangles inside the neurons, appears approximately 11 years before the clinical onset and that signs of neuronal death appear about 9 years earlier.”

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The consolidated theses

Rpssini continues: “It also consolidates the thesis according to which the loss of volume of some brain areas that undergo atrophy measurable with MRI appears approximately 8 years earlier, and finally testifies that the very first cognitive disorders verifiable with neuropsychological tests would appear approximately 6 years before the actual onset. It is well understood that compared to the moment of diagnosis there is a very long period of time during which the disease works in the dark and progresses. A period of time whose duration varies from subject to subject because it is balanced by resilience factors, such as the cognitive reserve and the neural reserve that each of us is equipped with. This last data is an element of growing interest on which we will soon focus.”

“No obvious predictive data”

In conclusion, Rossini highlights: “However, it should be underlined that the Chinese study does not provide any scientifically evident predictive data, in the sense that it does not allow a highly sensitive and specific instrument to predict with high accuracy (let’s say above 90%) which is very high risk or otherwise of developing the disease.
An additional element of knowledge published in a highly prestigious magazine, but nothing that will soon change the lives of our patients and their families, nor the healthcare organization to combat the disease”.

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Women are twice as likely as men

Finally, from another study, carried out by the researchers of Case Western Reserve Universityat the head of which he figures David Kang and published in the magazine Cellit turned out that women get Alzheimer’s disease about twice as often some men. A possible explanation for this greater vulnerability would be given by the fact that women show higher tau protein deposition in the brain. Because the process of eliminating excess tau begins with the addition of ubiquitin to the tau protein.

Because disruption of this process can lead to abnormal accumulation of tau, Kang and the study’s co-senior author Jung-A Woo they looked for increased activity of enzyme systems that add or remove the ubiquitin tag. And they found that both female mice and same-sex humans naturally express higher levels of the USP11 enzyme in the brain than males, and that this is linked to brain tau pathology in females, but not males.

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