Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease

Abstract

Significance Beta-amyloid plaque accumulation, glucose hypometabolism, and neuronal atrophy are hallmarks of Alzheimer’s disease. However, the regional ordering of these biomarkers prior to dementia remains untested. In a cohort with Alzheimer’s disease mutations, we performed an integrated whole-brain analysis of three major imaging techniques: amyloid PET, [ 18 F]fluro-deoxyglucose PET, and structural MRI. We found that most gray-matter structures with amyloid plaques later have hypometabolism followed by atrophy. Critically, however, not all regions lose metabolic function, and not all regions atrophy, even when there is significant amyloid deposition. These regional disparities have important implications for clinical trials of disease-modifying therapies.

Keywords

Affiliated Institutions

• Columbia University Irving Medical Center US
• Harvard University US
• The University of Melbourne AU
• University of California, Los Angeles US
• Neurology, Inc US
• San Francisco VA Medical Center US
• University College London GB
• Indiana University – Purdue University Indianapolis US
• UK Dementia Research Institute GB
• Emory University Hospital US
• Brown University US
• Edith Cowan University AU
• UNSW Sydney AU
• Austin Health AU
• Cancer Research And Biostatistics US
• Massachusetts General Hospital US
• Mental Health Research Institute AU
• University of Pittsburgh US
• Indiana University School of Medicine
• Bipar FR
• University of California, San Diego US
• University of Michigan US
• Alzheimer’s Disease Neuroimaging Initiative US
• University of California, San Francisco US
• Washington University in St. Louis US
• Mayo Clinic in Arizona US
• Neuroscience Research Australia AU
• University Radiology US

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