Seropositivity to Herpes Simplex Virus Antibodies

and Risk of Alzheimer’s Disease: A Population-Based

Cohort Study

PLoS ONE 2008; 3(11): e3637.

doi:10.1371/journal.pone.0003637

Luc Letenneur
INSERM U 897, Bordeaux, France
Luc.letenneur@inserm.fr
 Epidemiological data
• Renvoize (1987)
– no statistically significant difference in serum
antibody titres to HSV in a sample of 33 Alzheimer’s
disease (AD) patients and 28 controls.

• Ounanian (1990)
– in a sample of 19 AD patients and 21 controls, the
proportion of HSV-positive subjects was not different
between AD and control groups but increased titres
of anti HSV antibodies observed in the control group.
 The PAQUID study
• Longitudinal cohort of 3 777 subjects aged 65
years and older, living at home in South-west
France.
• Subjects were followed for 14 years with regular
cognitive evaluations.

• Sub-sample of 512 subjects with blood sample.

• Anti-HSV IgG and IgM antibodies assessment.

 Seropositivity status

• At baseline, 424 subjects (82.8%) were IgG

positive and 43 (8.4%) IgM positive.

• Only 86 subjects (16.8%) were both negative

for IgG and IgM.
 Baseline caracteristics
of the followed sample
Non Alzheimer Other
demented dementia
N 413 77 22
Age at entry 72.8 (5.8) 75.8 (6.0) 74.4 (5.7)
Women (%) 52.5 71.4 59.1
ApoE 4 20.7 29.3 31.8
IgG + (%) 81.1 89.6 90.9
IgM + (%) 7.0 16.9 4.5
 Risk of AD among IgG+
• During the follow-up, 16.3% of IgG+ and 9.1%
of IgG- developed an AD.

HR 95% CI p-value
Ig G+ 1.67 0.75 – 3.73 0.21

Cox regression model controled for age, gender, educational level, ApoE, baseline cognitive
performance.
Cumulative probability of AD
according to IgG status
 Risk of AD among IgM+
• During the follow-up, 30.2% of IgM+ and 13.7% of
IgM- developed an AD.

HR 95% CI p-value
Ig M+ 2.55 1.38 – 4.72 0.003

Cox regression model controled for age, gender, educational level, ApoE, baseline cognitive
performance.

• No modification effect found with ApoE

Cumulative probability of AD
according to IgM status
 Discussion
• HSV reactivation (IgM+) is associated with a higher
risk of developing AD.

• No association found with other type of dementia

• The increased risk of AD is observed more than 7

years after the HSV reactivation
 Discussion
• Is HSV act as a trigger ?

• Is HSV increase inflammatory processes in brain ?

• Is HSV reactivation only a marker of Alzheimer

process ?