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Imaging Brain Beta-Amyloid in Asymptomatic Elderly Subjects

English title Imaging Brain Beta-Amyloid in Asymptomatic Elderly Subjects
Applicant Hock Christoph
Number 125378
Funding scheme Project funding
Research institution Abteilung für Psychiatrische Forschung Psychiatrische Universitätsklinik Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurology, Psychiatry
Start/End 01.08.2009 - 31.07.2014
Approved amount 537'000.00
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Keywords (7)

Dementia; Early Diagnosis; Positron emission tomography; Beta-Amyloid Imaging; PET; PIB; Alzheimer's disease

Lay Summary (English)

Lead
Lay summary
Alzheimer's disease is the most prevalent neurodegenerative disease with a considerable increase in incidence in the aging population. Alzheimer's disease affects approximately 100'000 individuals in Switzerland, 5 million in the United States and 15 million worldwide. The deposition of toxic beta-amyloid peptides is a central feature of the disease with the accumulation of beta-amyloid commencing as early as 30 years before the onset of initial clinical signs of dementia. This projects aims at investigating the frequency of brain beta-amyloidosis in asymptomatic elderly subjects by using Pittsburgh Compound B (PIB) PET-imaging. The role of brain beta-amyloidosis as a major risk factor for the conversion of asymptomatic elderly subjects to mild cognitive impairment, and finally to Alzheimer's disease, will be investigated, along with analysis of cognitive, MRI morphometric and cardiovascular parameters. This project may give important insights towards future prevention of Alzheimer's disease by beta-amyloid reducing therapies at the preclinical stage.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.
Steininger Stefanie C, Liu Xinyang, Gietl Anton, Wyss Michael, Schreiner Simon, Gruber Esmeralda, Treyer Valerie, Kälin Andrea, Leh Sandra, Buck Alfred, Nitsch Roger M, Prüssmann Klaas P, Hock Christoph, Unschuld Paul G (2014), Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System., in Frontiers in aging neuroscience, 6, 52-52.
Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer's disease.
Kälin Andrea M, Pflüger Marlon, Gietl Anton F, Riese Florian, Jäncke Lutz, Nitsch Roger M, Hock Christoph (2014), Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer's disease., in Frontiers in aging neuroscience, 6, 147-147.
Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype.
Riese Florian, Gietl Anton, Zölch Niklaus, Henning Anke, O'Gorman Ruth, Kälin Andrea M, Leh Sandra E, Buck Alfred, Warnock Geoffrey, Edden Richard A E, Luechinger Roger, Hock Christoph, Kollias Spyros, Michels Lars (2014), Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype., in Neurobiology of aging, 30-30.
Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects.
Schreiner Simon J, Liu Xinyang, Gietl Anton F, Wyss Michael, Steininger Stefanie C, Gruber Esmeralda, Treyer Valerie, Meier Irene B, Kälin Andrea M, Leh Sandra E, Buck Alfred, Nitsch Roger M, Pruessmann Klaas P, Hock Christoph, Unschuld Paul G (2014), Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects., in Frontiers in aging neuroscience, 6, 240-240.

Collaboration

Group / person Country
Types of collaboration
Clinic for Nuclear Medicine, University Hospital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
University of Pittsburgh United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Clinic for Cardiology Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
112616 Role of antibodies against amyloid beta-peptides in alzheimer's disease 01.05.2006 Project funding
124111 The conversion of mild cognitive impairement to alzheimer's disease 01.07.2009 SPUM

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease with a considerable increase in incidence in the aging population. Beta-amyloid pathology is a central feature of the neuropathology in AD, with the build-up and accumulation of beta-amyloid commencing as early as 30 years before the onset of initial clinical signs of dementia, as suggested by neuropathological studies. Pittsburgh Compound B (PIB) PET-imaging can reiably detect brain beta-amyloidosis in living subjects. Because of the known conversion of PIB-positive subjects with mild cognitive impairment to clinically manifest AD, the presence of PIB-positive brain beta-amyloidosis can be considered a major risk factor for the development of dementia. Human brain aging occurs both with and without the development of progressive brain beta-amyloidosis, and it is hypothesized that the development of progressive beta-amyloidosis is a preclinical, prodromal state of Alzheimer’s disease that will eventually become clinically manifest. The factors, however, contributing to progressive brain beta-amyloidosis occurring during normal aging are unknown. This research program is designed to compare PIB-positive healthy elderly subjects with brain beta-amyloidosis to matched PIB-negative elderly subjects without brain beta-amyloidosis and to determine whether cognitive, genetic (ApoE4), cardiovascular (lipids, cholesterol, blood pressure, obesity), prior episodes of brain disease (ischemia, trauma, depression) and structural (brain atrophy) factors correlate with PIB-positive PET scans. In a further planned study, we plan to re-mage study participants with PIB-PET three years following the initial scan in order to determine that rates of progression of brain beta-amyloidosis over time.The program will test the following Working Hypotheses: (1) that brain beta-amyloidosis is occurring more frequently in ApoE4-positive subjects as well as in subjects with cardiovas-cular risk factors or brain trauma, (2) that brain beta-amyloid is associated with initial signs of compromised cognitive functions compatible with mild cognitive impairment (MCI), and (3) that brain beta-amyloidosis is associated with initial signs of brain atrophy.The Specific Aims of this project are:1.To characterize differences is cognitive functions in healthy elderly subjects with and without brain beta-amyloidosis.2.To determine whether ApoE genotype or cardiovascular risk factors are associated with brain beta-amyloidosis in healthy elderly subjects.3.To determine the effects of prior episodes of such brain diseases as ischemia, depression or trauma are associated with brain beta-amyloidosis.4.To determine whether brain-beta amyloidosis is associated with MRI signs of brain atrophy. Experimental Design and Methods - To achieve these aims, we will recruit 100 healthy elderly subjects aged 55 to 70 with subjective memory complaints but with no clinical signs of dementia. In collaboration with the Department of Nuclear Medicine (Profs. Gustav von Schulthess and Freddi Buck) we will perform PET-Imaging of PIB radiochemically synthesized under GMP condition in collaboration with Prof. P. August Schubiger at the Center for Radiopharmaceutical Science of ETH, PSI and USZ. Initial signs of progressively compromised cognition will be determined both upon inclusion and 18 months later by standardized neuropsychological test batteries normalized for the healthy elderly population. Cardiovascular risk factors will be analyzed in collaboration with Prof. Thomas Lüscher by using a standardized battery of blood tests, clinical examinations and anam-nestic investigations. The history of prior brain diseases will be validated though patient record files, and signs of progressive brain atrophy will be determined by using MRI brain volumetry with a period of 18 months. Expected value - The results generated by these studies will identify factors that influence the development of brain beta-amyloidosis in healthy elderly subjects. Should it turn out that brain beta-amyloidosis is associated with signs of compromised cognition or signs of brain atrophy, this population of elderly subjects could become a prime target population for primary prevention of Alzheimer’s disease by using beta-amyloid-reducing therapy.
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