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Early detection of amyloid load using 18F-florbetaben PET

Journal Article · · Alzheimer's Research & Therapy
 [1];  [2];  [3];  [4];  [5];  [6];  [3];  [7];  [7];  [8];  [2];  [2];  [2];  [2];  [9];  [3];  [2];  [10];  [11];  [12] more »;  [3] « less
  1. Life Molecular Imaging GmbH, Berlin (Germany); OSTI
  2. Life Molecular Imaging GmbH, Berlin (Germany)
  3. Universitat Internacional de Catalunya (UIC), Barcelona (Spain). Fundació ACE Institut Català de Neurociències Aplicades. Research Center and Memory Unit; Instituto de Salud Carlos III, Madrid (Spain). Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED)
  4. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Univ. Hospital Leipzig (Germany). Dept. of Nuclear Medicine
  6. Univ. of Pittsburgh, PA (United States). Dept. of Psychiatry; Univ. of Melbourne (Australia). Austin Health. Depts. of Medicine and Molecular Imaging
  7. Universitat Internacional de Catalunya (UIC), Barcelona (Spain). Fundació ACE Institut Català de Neurociències Aplicades. Research Center and Memory Unit
  8. Univ. of Melbourne (Australia). Austin Health. Depts. of Medicine and Molecular Imaging; Commonwealth Scientific and Industrial Research Organization (CSIRO), Melbourne, VIC (Australia). The Australian e-Health Research Centre. Health and Biosecurity
  9. Life Molecular Imaging Inc, Boston, MA (United States)
  10. Univ. of Melbourne (Australia). Austin Health. Depts. of Medicine and Molecular Imaging
  11. Univ. Hospital Leipzig (Germany). Dept. of Nuclear Medicine
  12. Invicro, New Haven, CT (United States)
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A low amount and extent of Aβ deposition at early stages of Alzheimer’s disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition. The study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition (“gray zone”), and subjects with established Aβ pathology. SUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the “gray zone” or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology. This study supports the utility of using two cutoffs for amyloid PET abnormality defining a “gray zone”: a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1816049
Journal Information:
Alzheimer's Research & Therapy, Journal Name: Alzheimer's Research & Therapy Journal Issue: 1 Vol. 13; ISSN 1758-9193
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
Alzheimer’s disease
Amyloid-beta
Florbetaben
Mild cognitive impairment
PET
Subjective memory complainers