Innovative Biomarkers in Alzheimer's Disease and Frontotemporal Dementia (FTD): Preventative and Personalized

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01403519
Recruitment Status : Unknown
Verified July 2011 by Rambam Health Care Campus.
Recruitment status was:  Not yet recruiting
First Posted : July 27, 2011
Last Update Posted : July 27, 2011
Information provided by:
Rambam Health Care Campus

Brief Summary:

Tau pathology and tangles have been associated with cognitive dysfunction causing neurodegeneration. AD, the most abundant tauopathy is characterized by amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases including frontal atrophy associated with cognitive clinical dysfunction of frontal dysexecutive syndrome, progressive nonfluent aphasia and semantic dementia as recently reviewed (Gozes 2010). It is the investigators aim to follow other protein expression [as per recent publications (Marksteiner et al., 2011)] in blood and CSF samples from those tauopathies.

Significance: Results should establish the possibility of using tau and other proteins as markers for early detection and disease progression in FTD, also in comparison to Alzheimer's disease (AD).

Condition or disease
Alzheimer's Disease

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Detailed Description:

Assessing biomarkers in Alzheimer's disease and frontotemporal dementia

  1. Specific Aims

    To enhance the field of biomarker recognition and facilitate preventative and personalized medicine we are now posing the following question, does the Israeli patient population present similar plasma protein profile as described before for other populations (Marksteiner et al., 2011).

    Studies will be carried out by RNA transcript quantification, quantitative real time polymerase chain reaction (blood cells and CSF) and immunochemical detection at the protein level (CSF and serum).

  2. Methods:


Human lymphocytes are isolated from 10 ml of venous blood using the Ficoll Paque method (de Rock and Taylor 1977; McCauley and Hartmann, 1982), for RNA extraction and determinations we shall follow-up the methods described in our manuscripts (Dresner et al., 2011).

Blood plasma and serum will be prepared as outlined in Protein quantitation will be carried out using the Tri reagent (Sigma) which allows for simultaneous preparation of RNA, DNA and protein and plasma immunodepletion and albumin depletion kits from Sigma.

Protein quantification: this will be carried out on cellular proteins and also on plasma proteins by SDS-polyacrylamide gel electrophoresis, followed by western analysis.

CSF samples will be collected through a spinal needle inserted into the L4-L5 or L3-L4 vertebral space with the subject in the lateral decubitus position. One ml of CSF derived from each patient will be immediately immersed in ice, with subsequent maintenance at -70 degrees C (or in dry ice during shipping) until the time of the assay. Half ml of each CSF sample will be concentrated by lyophilization in a Speed-Vac (Holten, Gydevang, Denmark) to about 0.1ml. CSF protein immunoblotting will be performed using a similar methodology as described above [and see also(Kozlovsky et al., 2004)]. Protein expression will be analyzed by western blots (Shiryaev et al., 2010).

Number of patients:

We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.

Professor Aharon-Peretz will evaluate patients with suspected Alzheimer's disease and frontotemporal dementia and include patients at various disease stages in a stratified manner (mild, moderate and severe). All patients will have signed an informed consent form, as per Helsinki guidelines. Clinical evaluation will include: physical and neurological evaluation. All patients will be asked to donate 50 ml blood and selected patients will undergo lumber puncture. The lumber puncture will be performed with the neurological work up. Professor Gozes will coordinate the scientific aspect of the study.

Study coordinators:

Scientific: Professor Illana Gozes, PhD, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Director, The Adams Super Center for Brain Studies, Tel Aviv University: Clinical material: Professor Judith Aharon-Peretz, MD, Head of "Cognitive Neurology Unit" Rambam Rambam-Health Care Campus, Haifa, Israel

Study Type : Observational
Estimated Enrollment : 70 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Innovative Biomarkers in Alzheimer's Disease and Frontotemporal Dementia (FTD): Preventative and Personalized
Study Start Date : July 2011
Estimated Primary Completion Date : January 2014
Estimated Study Completion Date : January 2014

Alzheimer's disease patients
Patients blood and CSF samples
Control group
Blood and CSF samples
FTD patients
Blood ad CSF samples

Biospecimen Retention:   Samples Without DNA
Blood and CSF

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
We estimate that about 30 patients with Alzheimer's disease, 20 patients with frontotemporal dementia and 20 controls will be included.

Inclusion Criteria:

  • Minimal cognitive impairment (MCI) and Alzheimer's disease (AD) patients, men and women, age 45-80 will be asked to participate in the present study.
  • MCI will be diagnosed when on cognitive evaluation the patients will score <1.5 SD on memory tests and will not be demented. AD will be diagnosed according to NINCDS-ADRDA research criteria. Patients will be stratified by age and cognitive (dementia) status. Disease severity for AD: mild to moderate (MMSE >16) AD.
  • Frontotemporal dementia: patients with a clinical diagnosis of frontotemporal dementia [behavioral variants (bv)FTD, progressive nonfluent aphasia (PNFA), or semantic dementia] and the related syndromes corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) will be included.
  • Inclusion criteria (controls): men and women, ages 45-80, willing to participate in the study and donate a blood samples.

Exclusion Criteria:

  • (patients and controls):

    1. Subjects unable/unwilling to sign an informed consent.
    2. Patients with associated medical condition: alcoholism, immune diseases and end stage medical conditions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01403519

Rambam Hospital Not yet recruiting
Haifa, Israel, 31096
Contact: Judith Aharon-Peretz, M.D.    972-4-8542637   
Sponsors and Collaborators
Rambam Health Care Campus
Principal Investigator: Judith Aharon-Peretz, M.D. Rambam Hospital, Haifa, Israel
Principal Investigator: Illana Gozes, Ph.D. Tel Aviv University, Sackler School of Medicine, Israel

Responsible Party: Prof' Judith Aharon-Peretz, Rambam Medical Center Identifier: NCT01403519     History of Changes
Other Study ID Numbers: 437-10CTIL
First Posted: July 27, 2011    Key Record Dates
Last Update Posted: July 27, 2011
Last Verified: July 2011

Additional relevant MeSH terms:
Alzheimer Disease
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms