In Reply Dr Zuckerman and colleagues are concerned that the definition of CTE used in our study was overly sensitive. The definitive diagnosis of Alzheimer disease, Lewy body disease, or CTE is based on strictly defined neuropathologic criteria.1- 3 In CTE and Lewy body disease, there is a pathognomonic lesion or a unique pathologic feature that is specific to the disorder and not found in healthy control patients. In Lewy body disease, the pathognomonic feature is the Lewy body, and a diagnosis is made even if only a single Lewy body is found.2,4 In CTE, the pathognomonic lesion is a cluster of tau-immunostained neurofibrillary tangles and neurites around a small vessel,3 and again, 1 lesion is sufficient for a pathologic diagnosis. The situation is analogous to finding a single microscopic focus of tumor—even a single small focus of tumor is sufficient for a diagnosis. Of the 177 CTE cases reported in our study, only 11 (6%) had 1 or 2 isolated CTE lesions and were considered stage I CTE; most cases (133 [75%]) showed advanced pathology and were stage III and IV. Unlike CTE and Lewy body disease, the diagnosis of Alzheimer disease requires the presence of 2 pathologic features, amyloid-β plaques and neurofibrillary tangles, distributed throughout the brain. Small amounts of amyloid-β plaques or neurofibrillary tangles are not sufficient for the diagnosis of Alzheimer disease... Keywords: American football
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", language="en", issn="0098-7484", doi="10.1001/jama.2017.16687", url="http://dx.doi.org/10.1001/jama.2017.16687" }