Objective: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [ 18 F]-flutemetamol and the level of amyloid-β measured by immunohistochemical (IHC) and histochemical (HC) staining in a frontal or parietal cortical region biopsy site. Background The development of molecular imaging techniques to 9visualize9 amyloid in vivo represents a major achievement in the study of Alzheimer9s disease (AD). Design/Methods: Forty nine patients with suspected Normal Pressure Hydrocephalus (NPH) underwent prospective (n=27) or retrospective (n=22) [ 18 F]-flutemetamol PET and cortical brain biopsy during intracranial pressure measurement or ventriculo-peritoneal shunting. [ 18 F]-Flutemetamol uptake was quantified using standardized uptake value ratio (SUVR) with cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowksy silver stain, and an overall pathology result based on all available IHC and HC results. Results: [ 18 F]-Flutemetamol SUVRs from the biopsy site were significantly associated with biopsy specimen amyloid-β levels using 4G8 (Pearson9s r=0.41, p=0.005). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [ 18 F]-flutemetamol in the region contralateral to the biopsy site (r=0.42, p=0.004), or with composite cortical [ 18 F]-flutemetamol uptake (r=0.44, p=0.002). Blinded visual assessment (BVA) of images showed a high level of agreement between all readers (κ=0.86). Using the overall pathology result as the standard of truth, BVA of PET images showed by-reader sensitivities of 100%, 71%, and 93%; specificity was 100% for each reader. Overall sensitivity and specificity by majority read were 93% and 100%, accordingly. Conclusions: [ 18 F]-Flutemetamol detects brain amyloid-β in vivo , demonstrates the strong concordance of [ 18 F]-flutemetamol PET imaging with histopathology irrespective of timing and sequence of examinations in prospective and retrospective settings, and shows promise as a valuable tool to study and possibly facilitate diagnosis of AD both in patients with suspected NPH, and among the wider population. Supported by: GE Healthcare, Princetone, NJ. Disclosure: Dr. Wolk has nothing to disclose. Dr. Rinne has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Leinonen has nothing to disclose. Dr. Arnold has received personal compensation for activities with Bristol-Myers Squibb Company and Cowan Group as a consultant. Dr. Arnold has received = research support from Penn-Pfizer Alliance, National Philanthropic Trust, Johnson & Johnson, Baxter, American College of Radiology Imaging Network, Pfizer Inc, and Eli Lilly & Company. Dr. Buckley has nothing to disclose. Dr. Smith has nothing to disclose. Dr. McLain has nothing to disclose. Dr. Sherwin has received personal compensation for activities with GE Healthcare as an employee. Dr. Sherwin has received research support from GE Healthcare. Dr. Farrar has nothing to disclose. Dr. Kailajarvi has nothing to disclose. Dr. Grachev has received personal compensation for activities with GE Healthcare as an employee.