Conference Coverage
COPENHAGEN—About 37% of APOE4 noncarriers with a primary clinical diagnosis of mild to moderate Alzheimer’s disease had nonexistent or sparse neuritic plaques, and 13% of APOE4 carriers had nonexistent or sparse neuritic plaques, researchers reported at the 2014 Alzheimer’s Association International Conference.
“Over one-third of APOE4 noncarriers with clinically mild to moderate Alzheimer’s disease dementia had minimal evidence of fibrillar amyloid-beta pathology,” stated Sarah E. Monsell, a biostatistician at the National Alzheimer’s Coordinating Center (NACC), University of Washington in Seattle, and colleagues, in a poster presented at the meeting.
Sarah E. Monsell
The researchers sought to determine the percentage of APOE4 noncarriers who had a primary clinical diagnosis of mild to moderate Alzheimer’s disease near the end of life and minimal amyloid-beta plaques at autopsy. The investigators also sought to evaluate the extent to which these cases were associated with appreciable tau pathology or a primary neuropathologic diagnosis other than Alzheimer’s disease.
The participants were recruited from the National Institute on Aging–funded Alzheimer’s Disease Center. Subjects had a primary clinical diagnosis of probable Alzheimer’s disease dementia at last visit and mild to moderate dementia defined as a Mini-Mental State Examination score of 16 to 26. Participants were assessed using the NACC Uniform Data Set between 2005 and 2012. In addition, all participants had a time between assessment and death of less than two years and neuropathology data available, as well as a known APOE genotype. One hundred APOE4 noncarriers were compared with 100 APOE4 carriers.
Among APOE4 noncarriers, 63% had moderate or frequent neuritic plaques, compared with 87% of APOE4 carriers. The researchers also found that 44% of APOE4 noncarriers with nonexistent or sparse neuritic plaques had extensive tau pathology, and 54% of APOE4 noncarriers with nonexistent or sparse neuritic plaques had a primary neuropathologic diagnosis other than Alzheimer’s disease.
Among APOE4 noncarriers with a clinical diagnosis of mild to moderate Alzheimer’s disease and nonexistent or sparse neuritic plaques, 46% had a primary neuropathologic diagnosis of Alzheimer’s disease, 5% had Alzheimer’s disease pathology present but insufficient for diagnosis, 8% had a normal brain, 8% had Lewy body disease, 14% had vascular disease, 5% had frontotemporal lobar degeneration, 8% had hippocampal sclerosis, 3% had Rosenthal fiber encephalopathy, and 3% had nigral degeneration with focal tauopathy.
—Colby Stong