Herpes Infections May Bring Forward The Onset Of Dementia

Scientists have investigated whether previous infections with viruses from the herpes family (such as mononucleosis or cold sores) may be linked to Alzheimer's. They found that healthy people who have previously had these viruses have higher blood levels of substances associated with the disease, even without symptoms. This suggests that common infections throughout life may influence the future risk of developing dementia.

Alzheimer's is the most common form of dementia in older adults, but to date, scientists still don't know exactly what causes this disease in its most common form, sporadic, which appears without a clear hereditary cause.

Some risk factors have already been identified: for example, a genetic variation called apoE4 increases the chance of developing Alzheimer's. Lifestyle also plays a role; diet, exercise, sleep, and other healthy habits can influence risk.

However, many experts believe that certain "attacks" on the body, such as infections or inflammation, may also play an important role in the development of the disease.

Among these possible factors is exposure to certain viruses, especially human herpesviruses (HHVs). These are very common viruses, such as cold sores, chickenpox, and cytomegalovirus, and many of us have come into contact with them at some point in our lives.

Some previous studies have found signs of these viruses in the brains of people with Alzheimer's. Furthermore, there is research suggesting that antiviral medications may help reduce the risk of dementia, which lends further support to this hypothesis.

In recent years, science has made significant progress in the search for blood tests that can help identify Alzheimer's even before symptoms appear. These tests look for substances called biomarkers, which are signals in the blood linked to brain changes characteristic of the disease.

The main biomarkers studied are the proteins beta-amyloid (Aβ40 and Aβ42) and phosphorylated tau (pTau181 and pTau217), which are associated with the formation of plaques and tangles in the brain, hallmarks of Alzheimer's. It is already known that these substances can be detected in the blood up to 20 years before symptoms appear. 

In this new study, researchers at the University of Minnesota Medical School, USA, wanted to investigate whether previous contact with herpesviruses could be linked to changes in the levels of these biomarkers in the blood, even in people who do not yet have any cognitive problems (i.e., are cognitively healthy).

To do this, they analyzed blood samples from 345 collections made from 167 women between the ages of 26 and 98. In each sample, they measured the levels of the five biomarkers mentioned and also checked whether the person had antibodies against six types of herpesviruses, which indicate previous infection.

What they found was that, as age increased, the levels of these biomarkers also increased, which is expected, since the risk of Alzheimer's increases with age. However, this increase was much more pronounced in people who had antibodies to herpesviruses.

Frequency of appearance of the five Alzheimer's biomarkers used in the analyzed samples. (A) Aβ40 (N=323) (B) Aβ42 (N=323); (C) Aβ42/Aβ40 (N=311); (D) pTau181 (N=345); (E) pTau217 (N=345).

In particular, Epstein-Barr virus (HHV4, the same as mononucleosis) and HHV6 were most associated with this increase in biomarkers. HHV3 (chickenpox) was present in all samples, so it was not possible to evaluate its comparative effect.

In general, the biomarkers that increased the most were, in this order: Aβ40, Aβ42, pTau217 and pTau181. And among the viruses, those most associated with the increase were: HHV4, HHV6, HHV1 (herpes simplex type 1), HHV2 (genital herpes) and HHV5 (cytomegalovirus).

Human herpesviruses are associated with more pronounced, age-dependent increases in serum biomarkers of dementia in women without cognitive impairment. Mean increase (among HHV) in the Spearman correlation of the biomarker versus age in HHV(+) compared to HHV(−) for the four biomarkers presented.

Numerically, the mean increase in biomarkers in people who had previously had herpesviruses was more than double that in people who had never had them, a difference considered statistically significant.

Interestingly, the presence of the apoE4 gene, a known risk factor for Alzheimer's, did not affect this result.

These findings suggest that a previous infection with a herpesvirus can leave "marks" in the body that, over time, increase the levels of substances linked to Alzheimer's in the blood, even in people without symptoms. This reinforces the idea that common viruses, even those that apparently caused only mild infections in the past, may play an important and still underestimated role in the onset of dementia.

READ MORE:

Human herpes viruses are associated with steeper age-dependent increases of serum biomarkers for dementia in cognitively unimpaired women

Lisa M. James, George Stratigopoulos, and Apostolos P. Georgopoulos 

Scientific Reports, volume 15, Article number: 25475 (2025)

https://doi.org/10.1038/s41598-025-10102-1 

Abstract: 

Blood biomarkers for dementia are being increasingly used for screening and possibly early detection of dementia in cognitively unimpaired (CU) people. Here we measured blood serum levels of 5 dementia-related biomarkers (Aβ1–40 [Aβ40], Aβ1–42 [Aβ42], Aβ42/Aβ40 ratio, phosphorylated Tau181 [pTau181], and phosphorylated Tau217 [pTau217]) and determined the seroprevalence of 6 HHV (HHV1, HHV2, HHV3, HHV4, HHV5, HHV6) in 345 samples drawn at successive visits from 167 CU women 26–98 years old. All biomarkers except for Aβ42/Aβ40 increased significantly with age, particularly in those who were HHV seropositive. With respect to the biomarkers, the increase was highest for Aβ40 > Aβ42 > pTau217 > pTau181, and, with respect to HHV, the increase was highest for HHV4 > HHV6 > HHV1 > HHV2 > HHV5 (HHV3 was seropositive in all samples). Overall, the average normalized rate of increase of biomarkers with age was 2.15 × higher in the HHV seropositive vs. seronegative groups (P = 0.003, paired samples t-test). The presence of apolipoprotein E4 (apoE4) genotype did not have a significant effect on those rates. These findings document a link between prior viral infection and dementia-related blood biomarkers, adding support to the HHV hypothesis in developing dementia, irrespective of apoE4 allele presence.