P3-178: Diffuse and neuritic plaques, neurofibrillary tangles, and APOE genotype in preclinical AD

Abstract

A recent study indicated that, among individuals with autopsy–diagnosed AD, participants who were nondemented within one year prior to death were more likely to have frequent diffuse plaques on autopsy than frequent neuritic plaques, whereas demented participants were more likely to have frequent neuritic plaques than frequent diffuse plaques. Nondemented participants were further characterized by a greater likelihood of having frequent neurofibrillary tangles and at least one APOE e4 allele. To further explore the respective roles of diffuse plaques, neuritic plaques, neurofibrillary tangles, and APOE genotype in preclinical dementia. Participants (aged 65+ years at death) meeting Khachaturian (N=1,009), Low, Intermediate, or High Likelihood for NIA/Reagan (N=1,704), or Possible, Probable, or Definite CERAD (N=1,835) neuropathological criteria for AD with data in the National Alzheimer's Coordinating Center Minimum (MDS) and Neuropathology (NDS) Data Sets made up the study samples. In generalized linear mixed models (using the logit link function and adjusting for Alzheimer Disease Center effects) which included variables reflecting the frequency of neuritic plaques, diffuse plaques, and neurofibrillary tangle stage, tangles were associated with receiving a dementia diagnosis within one year of death in the three samples. Frequency of neuritic plaque pathology was related to receiving a dementia diagnosis within one year of death in samples defined using NIA/Reagan (F(2,1216)=6.72, p=.0013), CERAD (F(2,1187) =6.92, p=.0010) and Khachaturian (F(2,676)=2.87, p=.0575) criteria. Dementia was not associated with frequency of diffuse plaques in any sample. Similar models using APOE genotype instead of the neuropathological variables indicated that APOE genotype also predicts dementia. APOE genotype is associated with the likelihood of having frequent tangles, and neuritic plaques, but not diffuse plaques, in each sample. Preliminary data suggest that a premorbid diagnosis of dementia among autopsy–diagnosed individuals with AD is associated with APOE genotype, and with degree of tangle and neuritic plaque, but not diffuse plaque, pathology. Diffuse plaques may, however, play an important role in AD development at earlier stages of the disease, in accordance with previous reports. More work is needed to determine whether relationships between neuropathology and dementia among individuals with preclinical AD can be explained by APOE genotype.