Rabinovici G, Ghosh P, Madison C, Corbetta C, Mormino E, Miller B, Grinberg L, Seeley W, Jagust W.
PIB+ Scans in Dementia Patients are Associated with High Post-Mortem Amyloid Burden.
Human Amyloid Imaging Abstract. 2012 Jan 1;
Objective: To compare PIB-PET signal during life with post-mortem amyloid burden in patients with dementia.
Methods: 6 dementia patients underwent PIB-PET (age6.2 ±1.4% ApoE4+) and autopsy (2.2 ±.3 years after PET, range 0.7-4.7). PIB DVR images were visually assessed as PIB+/PIB- blinded to clinical diagnosis. Global amyloid burden was measured with a PIB Index, and scans were quantitatively classified using thresholds - one derived from young controls (YC, age4.7 ±.3, PIB Index ≥.08) and a second from older controls (OC, age4.8 ±.7, PIB Index ≥.16) (Mormino011). Post-mortem assessment of amyloid included Aβ immunohistochemistry in4/16 patients and Bielschowsky staining in the other two. Neuritic plaques (NPs) were graded prospectively as CERAD absent, sparse, moderate or frequent, unadjusted for age. Diffuse plaques (DPs) and amyloid angiopathy were noted as present/absent based on retrospective review of autopsy reports.
Results: Primary pathologic diagnoses included: high-likelihood AD (4), mixed FTLD-Tau/AD (1), FTLD-Tau (3), FTLD-TDP (6), argyrophilic grain disease (1) and genetic prion disease (1). NPs were present in3%, DPs in9% and amyloid angiopathy in8% of patients. All CERAD-frequent patients were visually rated PIB+ (Figure),/5 were PIB+ based on the YC threshold and/5 were PIB+ applying the OC threshold. All patients with CERAD absent to moderate NPs were visually and quantitatively rated PIB-negative. All PIB+ patients had Braak Stage V-VI neurofibrillary pathology. In CERAD absent to moderate subjects, there was no difference in PIB Index between those with and without NPs (Mann-Whitney, p=0.72), DPs (p=0.44) or amyloid angiopathy (p=1.00).
Conclusion: PIB+ scans were associated with a high burden of pathology, corresponding to NIA-Reagan high-likelihood AD. These findings suggest high specificity when applying PIB for differential diagnosis, and potentially in preclinical detection of AD.