Proposals for re-evaluation of current autopsy criteria for the diagnosis of Alzheimer's disease.
Defining criteria for the postmortem diagnosis of Alzheimer's disease (AD) has proven difficult due to the phenotypical heterogeneity of the disease, the absence of a specific disease marker and an overlap of AD neuropathology with that observed in a number of nondemented aged individuals. Even though the role of plaques and tangles in the pathogenesis of AD remains undetermined, a host of clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers-particularly in the neocortex-are still to be considered the best morphological signposts for the disease. All currently used criteria for the neuropathologic diagnosis of AD have some weaknesses and need to be reestablished and revalidated. Multivariant analysis in a personal autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging of neuritic Alzheimer-type lesions, and less concordance with the National Institutes of Aging and Tierney criteria. We propose a set of histopathologic diagnostic criteria for both definite and preclinical AD that rely on various constellations of both different types of plaques, except diffuse amyloid deposits, and neurofibrillary tangles, in allocortical and isocortical areas considering their topographic pattern. This set of criteria encompasses phenotypic variations of the pathology and takes into account the chronic, progressive course of AD. It allows the detection of preclinical disease in subjects in whom dementia is not reported and includes those cases in the morphological gray zone between "normal" aging and full-fledged AD that practicing neuropathologists consider the most problematic. The set of criteria includes guidelines concerning tissue sampling and processing, and standardized staining methods that should allow neurologists to minimize interrater and interlaboratory variability in the assessment of morphologic lesions and the diagnosis of AD.
Jellinger
K A
KA
Ludwig Boltzmann Institute of Clinical Neurobiology, Lainz-Hospital, Vienna, Austria.
Bancher
C
C
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003245:Consensus Statements as Topic; D003937:Diagnosis, Differential; D018450:Disease Progression; D014644:Genetic Variation; D017408:Guidelines as Topic / Q000592:standards; D006801:Humans; D016874:Neurofibrillary Tangles / Q000473:pathology; D010641:Phenotype; D012720:Severity of Illness Index