Tdap and Biomarkers of Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
Recently, the Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination was added to the list of immunizations associated with lower incidence of dementia. Plasma-based biomarkers for AD are a welcome alternative to expensive and invasive testing for Alzheimer's; these biomarkers include assessment of amyloid and tau and neurofilament light protein that assesses non-specific neurodegeneration. The investigators will test for these biomarkers, as well as some immune parameters, administer Tdap then repeat the blood tests in six months.

Detailed Description
-----------------
A growing number of studies have consistently shown reduced incident risk of dementia associated with a variety of vaccinations. Most recently, data probes of medical claims from two large and disparate databases showed that vaccination for tetanus, diphtheria and pertussis (Tdap) was associated with a 42% decrease in dementia. Adult vaccination coverage remains low for most routinely recommended vaccines, including Tdap. This study will screen and qualify participants who do not meet the recommended frequency interval for Tdap vaccination. Participants will have consented to a review of their medical history (including vaccination history), a neurocognitive test and a battery of blood tests. Included in the blood testing will be plasma-based testing for amyloid, tau and neurofilament light protein. The study will be considered a pilot study; it will be an open-label trial. All participants will receive a single dose of the Tdap vaccine. Nine months after vaccination, participants will repeat the pre-vaccine blood tests. Primary objective will be the assessment of change in the Alzheimer's disease (AD) biomarkers. Bordetella pertussis (B. pertussis), the bacterium that causes whopping cough, is one of the targets of the Tdap vaccine. B. pertussis is a hypothesized infectious trigger of Alzheimer's disease (AD). A secondary objective of the study will be determination of present and past infection by B. pertussis via IgG testing as well as PCR of nasal swab and how this may relate to the Alzheimer biomarker responses to Tdap vaccination.

Official Title
-----------------
Evaluation of Tdap Vaccination and Plasma Biomarkers of Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease, Late Onset

Intervention / Treatment
-----------------
* Biological: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Immuno- competent Out of compliance for Tdap vaccine (none within 10 years). Ability of give informed consent. SAGE test 17 or greater Exclusion Criteria: Immuno- compromised In compliance for Tdap vaccination (within 10 years). Known allergy to components of the Tdap vaccine. SAGE test <17

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: single group assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tdap<br>Open label study, no placebo comparator | Biological: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine<br>* Tdap is a combination vaccine that protects against three potentially life-threatening bacterial diseases: tetanus, diphtheria, and pertussis (whooping cough).<br>* Other names: Tdap;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Amyloid | Amyloid peptides 42/40 ratio | start of study and 6 months | 
| Change in Plasma Tau | a brain-specific protein that may be expected to leak from brain interstitial fluid to the plasma compartment in Alzheimer's disease as well as its preclincial and prodromal stages. | start of study and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of B. pertussis | Nasal swab for the presence of B. pertussis | start of study and 6 months | 
| B. pertussis IgG | Blood test for history of B. pertussis | start of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tdap, Alzheimer's, biomarkers, B. pertussis, immune risk profile