
The results of this unprecedented study indicate that SARS-CoV-2 infection may be associated with an increase in brain pathology markers linked to Alzheimer's. Although it is not yet possible to confirm that COVID-19 causes the disease, these findings reinforce the hypothesis that systemic infections may accelerate neurodegenerative processes.
Exposure to infectious diseases throughout life has been associated with an increased risk of neurodegenerative diseases, such as Alzheimer's, as well as other systemic diseases.
Studies have already linked infections such as viral encephalitis, meningitis, influenza, pneumonia and viral intestinal infections to an increased risk of developing Alzheimer's disease.
In addition, research indicates that vaccines that prevent these infections may have a protective effect against these conditions. This may occur through several mechanisms, such as tissue damage during the acute phase of the infection or chronic inflammatory processes that affect the brain directly or indirectly.
However, to better understand this relationship, large, well-controlled studies are needed to differentiate whether infection is truly a direct risk factor or whether there are other factors in common between people who become ill and those who develop dementia.

The COVID-19 pandemic has provided a unique opportunity to study this relationship on a large scale, as millions of people around the world have been exposed to the virus over well-defined periods of time.
Although SARS-CoV-2 does not directly attack the brain, significant neurological impacts have been observed in people who have had the infection, even in those who have not required hospitalization.
This is due, in part, to the strong inflammatory response that the virus triggers in the body, which can persist long after the initial infection. Preliminary studies have already suggested an increase in the incidence of dementia among vulnerable groups who have had severe COVID-19.
Therefore, the pandemic can be seen as a “natural experiment” to investigate whether systemic infections can initiate or accelerate degenerative processes in the brain, increasing the risk of Alzheimer's in the future.
Given the aging of the population and the global impact of the pandemic, understanding this possible relationship has become a public health priority. There are now biomarkers in blood and cerebrospinal fluid (CSF) that can identify early signs of neurodegenerative diseases years before symptoms appear.
These biomarkers include reduced levels of the protein β-amyloid 42 (Aβ42), as well as changes in the ratio of β-amyloid 42 to β-amyloid 40 (Aβ42:Aβ40) and increases in phosphorylated tau (pTau).
These changes are indicative of abnormal protein accumulation in the brain, a key hallmark of Alzheimer's disease. Other biomarkers, such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), indicate activation of nervous system cells and neuronal damage.

Research shows that these changes in biomarkers can occur up to 18 years before a clinical diagnosis of Alzheimer's. Blood tests can now measure these biomarkers with high accuracy, making it possible to assess the effects of COVID-19 on brain health in people who do not yet have symptoms of dementia.
Previous studies have reported changes in these biomarkers in people who have had COVID-19, especially in the most severe cases. However, to better understand the relationship between SARS-CoV-2 infection and the risk of Alzheimer's, it is necessary to follow patients over time, including those who had mild or moderate infections.
To do this, researchers used data from the UK Biobank, a large database in the United Kingdom that gathers health information and laboratory tests from thousands of people. During the beginning of the pandemic (2020–2021), this database was used to monitor exposure to SARS-CoV-2 and its effects on the body.
The study analyzed blood samples from 1,252 participants before and after infection, comparing their biomarkers with those of a control group similar in age, sex and health status.
This allowed the evaluation of the possible impacts of COVID-19 on the brain without other risk factors, such as aging or genetic predisposition, interfering with the results.

The findings of this study suggest that SARS-CoV-2 infections may have profound and long-lasting effects on human health. Since the pandemic, persistently high levels of illness and death associated with COVID-19 have been reported.
However, the impact of mild and moderate infections on the risk of dementia has not yet been fully investigated. While this study cannot prove that COVID-19 causes Alzheimer’s, the results suggest that the infection may accelerate the accumulation of abnormal proteins in the brain, which may increase the risk of the disease in the future.
Previous research has suggested that viral infections may increase the risk of dementia, but this has not been explored specifically for SARS-CoV-2. To investigate this relationship, the researchers measured biomarkers linked to Alzheimer’s in the blood of volunteers from the UK Biobank before and after infection.
The results showed that people who had COVID-19 had a reduction in the Aβ42:Aβ40 ratio and, in the most vulnerable cases, also had lower levels of the protein β-amyloid 42 and higher levels of phosphorylated tau protein.
These changes were more pronounced in people who had been hospitalized or who already had hypertension before infection. In addition, these changes in biomarkers were associated with signs of brain degeneration on imaging tests, worse performance on cognitive tests and an overall perception of poorer health.
The researchers also found that the reduction in the Aβ42:Aβ40 ratio after infection was equivalent to four years of aging or 60% of the effect caused by inheriting a single allele of the APOE-ε4 gene, one of the main genetic risk factors for Alzheimer's.
This lower ratio is one of the earliest detectable changes in the preclinical stages of the disease. The most vulnerable participants showed even more significant changes, with further decreases in levels of β-amyloid 42 protein and greater increases in phosphorylated tau protein.
These changes were associated with Alzheimer’s-like brain patterns on MRI, poorer cognitive performance, and poorer overall health.
Although SARS-CoV-2 does not directly attack the brain, the infection triggers a strong inflammatory response in the body, which can persist even in mild to moderate cases.

Previous studies have suggested that systemic inflammatory events may be related to the development of dementia, as chronic inflammation can affect the function of the brain's defense cells, making it difficult to eliminate toxic proteins such as β-amyloid.
In addition, inflammation can damage the blood-brain barrier, allowing inflammatory substances to enter the brain. Some research suggests that this inflammation can stimulate the production of β-amyloid, contributing to the accumulation of plaques in the brain.
The results of this study indicate that SARS-CoV-2 infection may be associated with an increase in markers of brain pathology linked to Alzheimer's. Although it is not yet possible to confirm that COVID-19 causes the disease, these findings reinforce the hypothesis that systemic infections may accelerate neurodegenerative processes.
Understanding this relationship better is essential to anticipate the impacts of the pandemic on the neurological health of the population and, possibly, develop strategies to reduce future risks of dementia.
READ MORE:
Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection
Eugene P. Duff, Henrik Zetterberg, Amanda Heslegrave, Abbas Dehghan, Paul Elliott, Naomi Allen, Heiko Runz, Rhiannon Laban, Elena Veleva, Christopher D. Whelan, Benjamin B. Sun & Paul M. Matthews
Nature Medicine (2025)
Abstract:
Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections is unknown. Determining this is important for anticipating the potential future incidence of dementia. To begin to do this, we measured plasma biomarkers linked to Alzheimer’s disease pathology in the UK Biobank before and after serology-confirmed SARS-CoV-2 infections. SARS-CoV-2 infection was associated with biomarkers associated with β-amyloid pathology: reduced plasma Aβ42:Aβ40 ratio and, in more vulnerable participants, lower plasma Aβ42 and higher plasma pTau-181. The plasma biomarker changes were greater in participants who had been hospitalized with COVID-19 or had reported hypertension previously. We showed that the changes in biomarkers were linked to brain structural imaging patterns associated with Alzheimer’s disease, lower cognitive test scores and poorer overall health evaluations. Our data from this post hoc case–control matched study thus provide observational biomarker evidence that SARS-CoV-2 infection can be associated with greater brain β-amyloid pathology in older adults. While these results do not establish causality, they suggest that SARS-CoV-2 (and possibly other systemic inflammatory diseases) may increase the risk of future Alzheimer’s disease.
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