The objectives of this study are as follows:1) To determine the sensitivity and reproducibility of novel assays developed at the Janssen Prevention Center to detect anti-tau immune responses in the blood of individuals.2) To determine the…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study is the anti-tau immune response, which is
divided into: 1) the total concentration of anti-(phospho-)tau antibodies in
plasma and 2) the percentage of total peripheral (blood) B lymphocytes reactive
against tau, phosphorylated tau, tau oligomers and paired helical filament tau.
Secondary outcome
Secondary outcomes of the study are:
1. The (phospho-)tau concentration in plasma, platelets, or plasma exosomes
2. The concentration of other proteins or (total) Ig in plasma, platelets, or
plasma exosomes for purpose of sample normalization
Background summary
Alzheimer*s disease (AD) is pathologically defined by neurofibrillary tau
tangles and *-amyloid plaques in the brain. Recently, the Janssen Prevention
Center has isolated from peripheral blood of healthy and AD-affected
individuals B cells that possess surface immunoglobulin able to bind to the
microtubule binding protein tau. This pilot study will begin to investigate
whether individuals with AD have a more matured anti-tau immune response and/or
a response of greater magnitude relative to healthy control individuals. The
hypothesis is that individuals with AD, because their immune system has been
exposed to the altered forms of tau that accumulate in the brain during AD, may
make immune responses to those forms of tau. If changes in these immune
responses correlate with disease risk or progression then that might ultimately
allow diagnosis of AD with a blood test rather than via expensive imaging
procedures or via invasive collection of cerebrospinal fluid.
Study objective
The objectives of this study are as follows:
1) To determine the sensitivity and reproducibility of novel assays developed
at the Janssen Prevention Center to detect anti-tau immune responses in the
blood of individuals.
2) To determine the concentration of anti-(phospho-)tau antibodies in plasma of
healthy young individuals and aged individuals with subjective cognitive
decline.
3) To determine whether total concentration of anti-(phospho-)tau antibodies is
increased in plasma of AD patients compared to age-matched controls with
subjective cognitive decline.
4) To determine whether B lymphocytes reactive against tau species are
increased in early AD compared to age-matched controls with subjective
cognitive decline.
Study design
A cross-sectional study performed at the Alzheimer Center of the VU University
Medical Center (VUmc).
Study burden and risks
There are no direct benefits for the participants of the study. The risk
associated with participation can be considered negligible and the burden can
be considered minimal, since blood colletion by venipuncture is a frequently
performed, which is considered to be safe.
De Boelelaan 1118
Amsterdam 1081 HZ
NL
De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
Group 1: Alzheimer*s Disease
- Diagnosis of AD according to the NIA-AA criteria (McKhann 2011)
- MMSE score of 18-*27
- Have abnormal CSF *-amyloid concentration and/or *-amyloid PET evidence for AD pathology
- *50 years old;Group 2: Subjective Cognitive Decline
- No objective memory loss with normal results on neuropsychological tests and no other explanation for memory complaints.
- MMSE score of 27-30
- Normal CSF *-amyloid concentrations or *-amyloid PET imaging
- *50 years old;Group 3: Young healthy controls
- No memory complaints
- MMSE score of 27-30
- 18-30 years of age
Exclusion criteria
All groups
- History of concussion or other acute head trauma in the past six months
- Currently engaging in activity (e.g. rugby) likely to induce repetitive head trauma
- Stroke or other ischemic incident within the past six months
- Current or past diagnosis of autoimmune disease
- Current or past diagnosis of immunosuppressive disorder
- Ongoing or past (within the last 3 months) treatment with any immunosuppressive drug (e.g. prednisone)
- Ongoing or past (within the last 3 months) treatment with drugs (e.g. Anakinra) that suppress the interleukin-1, interleukin-6, or TNF-* response EXCEPT NSAIDs.
- Current or previous (within the past year) treatment for malignancy
- Current or previous diagnosis of hematological malignancy
- Recent transfusion or treatment with blood products such as IVIG
- Diagnosis of HIV, HBV, or HCV
- Judged not to be of sound mind and judgement;Additional exclusion criteria per research group:
Group 1:
- Any current medical or neurological condition other than AD that could explain the patient*s dementia
- Diagnosis of genetically proven familial AD;Groups 2 and 3:
- Current diagnosis of probable dementia of any etiology
- Current diagnosis of probable tauopathy of any etiology
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55460.029.15 |