A key protein in the brain could reveal if someone is likely to develop Alzheimer’s later in life, a study has revealed.
Researchers from Florida International University investigated the role of TSPO, a protein that serves as a biomarker of brain inflammation, to see when in life it increases and where it rises in the brain.
For the study, advanced imaging software was used to track TSPO levels in mice that were genetically modified to carry human gene mutations known to increase the risk of Alzheimer’s.
These models are used by scientists to study how the disease develops and to test potential treatments.
After studying TSPO and Alzheimer’s levels in mice, the scientists checked whether the same was observed in human brains that had been donated by members of the world’s largest group of individuals with early-onset Alzheimer’s, a community in Colombia.
In the mouse model, researchers detected elevated TSPO levels in the subiculum – a critical part of the hippocampus – as early as six weeks of age, roughly equivalent to age 18 to 20 in humans.
Microglia, the brain’s immune cells that cluster around amyloid plaques, harmful proteins that accumulate in the brains of Alzheimer’s patients, had the highest levels of TSPO.
Rebecca Luna was diagnosed with early-onset Alzheimer’s at 46. Now scientists are hopeful a key protein in the brain could reveal the likelihood of someone developing the disease so that preventative treatments can be administered
Amyloid plaques are a hallmark characteristic of Alzheimer’s disease and contribute to cognitive decline and memory loss.
Notably, female mice had higher TSPO levels, mirroring real-world statistics: two-thirds of Alzheimer’s patients are women.
The brain tissue samples from the Colombian patients with the rare genetic mutation (PSEN1 E280A), known as the paisa mutation, that almost always leads to early-onset Alzheimer’s, showed the same pattern.
This means that elevated levels of TSPO – as seen in medical imaging of the brain – could indicate a higher risk of developing Alzheimer’s.
People with strong genetic risk factors for Alzheimer’s show elevated TSPO early, which supports the theory that brain inflammation is an early driver of disease.
The researchers now want to look at this link further to better understand the role that TSPO plays.
They are unsure if it contributes to damage or protects the brain – and whether blocking or enhancing it could halt disease progression.
Lead researcher Dr Tomás Guilarte said: ‘This is the first study to really examine how early this biomarker increases and where it begins rising in the brain.
‘If we can use this information to help delay Alzheimer’s progression by even five years, it can drastically improve patients’ lives and reduce disease prevalence.’
Dr Guilarte is considered an internationally established expert on TSPO and he has studied the protein for more than three decades.
His work helped establish it as a reliable imaging biomarker used in diagnosing brain inflammation in various neurodegenerative, neurological and psychiatric disorders.
Even in late-stage Alzheimer’s, the researchers found that TSPO levels remained high in the immune cells in the brain (microglia) that are found close to amyloid plaques.
A cell image showing immune cells in the brain (microglia) (blue) signaling TSPO (red) and clustered around plaques (cyan)
Dr Guilarte’s previous study, published in JAMA Neurology, showed TSPO levels were higher in active and recently retired NFL players ranging in age from 23 to 39
The team is now working with a specially developed Alzheimer’s mouse model lacking TSPO to explore these questions further.
They’re also expanding the study to include sporadic, late-onset Alzheimer’s cases, the form that accounts for over 90 percent of all diagnoses.
‘The more we understand these processes,’ said Daniel Martínez Pérez, first author and Ph. candidate in Dr Guilarte’s lab, ‘the closer we get to tailoring treatments that can truly help – before it’s too late.’
He added: ‘One of the biggest problems with Alzheimer’s is people see it as a disease of aging and that impacts when people get diagnosed.
‘But the reality is that the disease starts decades before diagnosis and the more biomarkers and therapeutic targets our global community of scientists are finding, the closer we all get to physicians having a whole panel of diagnostics to be able to deliver more personalized, tailored treatments.
‘My hope is we can be part of helping people before they are too sick.’
Alzheimer’s is one of the most common forms of dementia and mostly affects adults over the age of 65.
About seven million people in the US aged 65 and older live with the condition, and over 100,000 die from it annually.
Alzheimer’s disease is the most common cause of dementia. The disease can cause anxiety, confusion and short-term memory loss
The Alzheimer’s Association estimates that by 2050, nearly 13million Americans will be living with the disease.
Early-onset Alzheimer’s affects a small subset of the population diagnosed with this memory-robbing form of dementia caused by shrinking brain tissue.
Five percent of the nearly seven million Americans with the disease are diagnosed between the ages of 45 and 65, well before the average diagnosis age of 80.
Early-onset Alzheimer’s is not solely Alzheimer’s disease at a younger age. It often runs in families. In some cases, it’s passed down directly from parent to child, while in others, people may inherit a mix of genes that increase their risk.
The disease tends to progress faster in people with an early-onset diagnosis compared to those who develop it later in life.
Even after accounting for the general risks of aging, people with early-onset Alzheimer’s have a higher risk of dying compared to those with late-onset or typical Alzheimer’s.
This causes a significant number of premature deaths in adults aged 40 to 64 caused by complications due to Alzheimer’s, like infections, seizures, and pneumonia caused by food or liquid enters the lungs instead of the esophagus.
The wide variety of causes of death means quantifying the annual death toll linked to the condition is difficult to pin down.
Still, about 120,000 people with Alzheimer’s, both typical and early-onset, died in 2022 (the most recent year for which data is available).
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