One in four patients with mild to moderate Alzheimer’s disease dementia had only scant evidence of neuritic amyloid plaques, and the finding was almost three times more common among apolipoprotein E epsilon-4 noncarriers than in carriers, researchers reported online in JAMA Neurology.
“These findings suggest that a nonamyloidogenic variant resembling the clinical phenotype of Alzheimer disease may be more common than previously expected … particularly in APOE4 [apolipoprotein E epsilon-4] noncarriers,” said Sarah Monsell of the University of Washington’s National Alzheimer’s Coordinating Center, Seattle, and her associates. Such patients might not respond to treatments targeting fibrillar or soluble amyloid-beta, the researchers said.
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Their study explored clinical and neuropathologic data from 100 APOE4 noncarriers and 100 APOE4 carriers who were diagnosed with mild to moderate Alzheimer’s disease (AD) at their last visit to an AD center. All patients had a Mini-Mental State Examination score of 16-26 and died within 24 months of their last evaluation (JAMA Neurol. 2015 Aug 24. doi: 10.1001/jamaneurol.2015.1721).
Fully 37% of APOE4 noncarriers had scant postmortem evidence of amyloid-beta peptide plaques, compared with only 13% of carriers, the investigators reported. Also, 45% of patients with sparse neuritic plaques had extensive (Braak stages III or IV) neurofibrillary degeneration, and most others met neuropathologic criteria for diseases related to dementia, including vascular disease, Lewy body disease, hippocampal sclerosis, frontotemporal lobar degeneration, and tangle-only dementia. “These findings support the results of recent PET imaging studies suggesting that many participants who meet clinical criteria for mild to moderate Alzheimer dementia do not appear to have high levels of amyloid-beta accumulation in the cerebral cortex,” the researchers wrote.
The National Institute on Aging and the Arizona Alzheimer’s Consortium funded the study. Two coauthors reported financial relationships with GE Healthcare, Avid Radiopharmaceuticals, Navidea Biopharmaceuticals, and Merck.