Neurofibrillary Tangles, Amyloid, and Memory in Aging and Mild Cognitive Impairment

TLDR

Large numbers of neurofibrillary tangles and amyloid plaques are hallmark markers of Alzheimer disease, yet NFTs are more closely linked to cognitive decline than amyloid, and it is unclear whether this relationship holds in normal aging and mild cognitive impairment. The study aimed to map the regional distribution of beta‑amyloid plaques and NFTs and to examine how these lesions associate with memory performance in nondemented elderly individuals and those with MCI. Eight nondemented participants who underwent annual neuropsychological testing and brain donation were examined to assess tangle and plaque burdens. Higher neurofibrillary tangle densities—particularly in medial temporal lobe regions—were found in MCI subjects and correlated with poorer memory scores, whereas amyloid plaque density varied and showed no such association, suggesting NFTs may underlie memory loss across aging, MCI, and Alzheimer disease.

Abstract

Large numbers of neurofibrillary tangles (NFTs) and amyloid plaques are diagnostic markers for Alzheimer disease (AD), but lesser numbers of these lesions are also seen in nondemented elderly individuals. Much of the existing literature suggests that the NFTs of AD have a closer correlation with cognitive function than do amyloid plaques. Whether a similar relationship exists in normal aging and mild cognitive impairment (MCI), a condition that frequently reflects a preclinical stage of AD, remains unknown.To determine the distribution patterns of beta-amyloid plaques and NFTs and the association of these lesions with memory performance in nondemented individuals.We investigated regional distributions and neuropsychological correlates of NFTs and amyloid plaques in cognitively normal elderly persons and subjects with MCI who received neuropsychological testing before death. Subjects Eight nondemented subjects who volunteered to receive annual neuropsychological testing and agreed to brain donation were studied. Five subjects showed no cognitive impairment, and 3 were diagnosed with MCI.Distribution of NFTs followed a rigorous and hierarchical pattern, but distribution of amyloid plaques varied among individuals. Subjects with MCI displayed higher NFT densities than did nonimpaired subjects. In addition, NFT density in the temporal lobe correlated with memory scores, whereas density of amyloid plaques did not.Neurofibrillary tangles are more numerous in medial temporal lobe regions associated with memory function and show a relationship to performance on memory tests in nondemented individuals. These results suggest that NFTs may constitute a pathological substrate for memory loss not only in AD but also in normal aging and MCI.