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In 1987, neuropathologists representing the charter group of CERAD clinics met to develop a practical instrument for standardizing the postmortem evaluation of the brains of individuals with Alzheimer's disease (AD) who had been enrolled in the multicenter CERAD study. At that time, standardized CERAD assessment batteries of the clinical and neuropsychological characteristics of this disorder had been established, and the need for a comparable evaluation of the neuropathologic findings had become apparent. Two years earlier, a panel of neuropathologists had recommended a set of minimal microscopic criteria for the diagnosis of AD.1 They suggested that the diagnosis be based on an age-related minimum number of senile plaques per microscopic field of neocortex. Although that report provided useful guidelines that had not been previously available, the criteria were arguably arbitrary and did not take into account differences in the stains and techniques used and variations in interpretation.
For these reasons, the CERAD neuropathologists formed a task force to develop more accurate and reliable neuropathologic criteria for AD, determine the neuropathologic spectrum of this disorder, and establish the types and frequency of coexisting disorders. A standardized neuropathologic protocol that involved a semiquantitative approach to assessment of the frequency of senile plaques, neurofibrillary tangles, and other changes was formulated and tested.2 The frequency of neocortical neuritic plaques is correlated with the patient's age to arrive at an "age-related plaque score," which, along with the clinical history of dementia, is used to establish a level of certainty for the diagnosis of AD (e.g., definite AD, probable AD, possible AD, and normal brain). The neuropathologic protocol includes a data entry form and illustrated guidebook with photomicrographs.
To further promote standardization, 24 neuropathologists from 18 medical centers participated in a study to determine the inter-rater reliability among laboratories for the …
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