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Absence of Pittsburgh Compound B Detection of Cerebral Amyloid β in a Patient With Clinical, Cognitive, and Cerebrospinal Fluid Markers of Alzheimer DiseaseA Case Report
Nigel J. Cairns, PhD;
Milos D. Ikonomovic, MD;
Tammie Benzinger, MD;
Martha Storandt, PhD;
Anne M. Fagan, PhD;
Aarti R. Shah, MS;
Lisa Taylor Reinwald, BA;
Deborah Carter;
Angela Felton, BS;
David M. Holtzman, MD;
Mark A. Mintun, MD;
William E. Klunk, MD;
John C. Morris, MD
Arch Neurol. 2009;66(12):1557-1562.
Background To date, there have been no reports of individuals who have been characterized longitudinally using clinical and cognitive measures and who transitioned from cognitive normality to early symptomatic Alzheimer disease (AD) during a period when both cerebrospinal fluid (CSF) markers and Pittsburgh Compound B (PiB) amyloid imaging were obtained.
Objective To determine the temporal relationships of clinical, cognitive, CSF, and PiB amyloid imaging markers of AD.
Design Case report.
Setting Alzheimer disease research center.
Participant Longitudinally assessed 85-year-old man in a memory and aging study who was cognitively normal at his initial and next 3 annual assessments.
Main Outcome Measures Serial clinical and psychometric assessments over 6 years in addition to PiB imaging with positron emission tomography (PET) and CSF biomarker assays before autopsy.
Results Decline in measures of episodic memory and, to a lesser degree, working memory began at about age 88 years. PiB PET amyloid imaging was negative at age 88 years, but at age 89 years there was reduced amyloid β 42 and elevated levels of tau in the CSF. Beginning at age 89 years, very mild cognitive and functional decline reported by his collateral source resulted in a diagnosis of very mild dementia of the Alzheimer type. After death at age 91 years, the autopsy revealed foci of frequent neocortical diffuse amyloid β plaques sufficient to fulfill Khachaturian neuropathologic criteria for definite AD, but other neuropathologic criteria for AD were not met because only sparse neuritic plaques and neurofibrillary tangles were present. Postmortem biochemical analysis of the cerebral tissue confirmed that PiB PET binding was below the level needed for in vivo detection.
Conclusion Clinical, cognitive, and CSF markers consistent with AD may precede detection of cerebral amyloid β using amyloid imaging agents such as PiB that primarily label fibrillar amyloid β plaques.
Author Affiliations: Alzheimer's Disease Research Center (Drs Cairns, Storandt, Fagan, Holtzman, Mintun, and Morris, Mrs Shah, and Mss Taylor Reinwald, Carter, and Felton) and Departments of Neurology (Drs Cairns, Benzinger, Storandt, Fagan, Holtzman, Mintun, and Morris and Mr Shah), Pathology and Immunology (Drs Cairns and Morris and Mss Taylor Reinwald, Carter, and Felton), and Radiology (Drs Benzinger and Mintun), School of Medicine, and Department of Psychology, School of Arts and Sciences (Dr Storandt), Washington University, St Louis, Missouri; and Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Drs Ikonomovic and Klunk).
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