The temporospatial evolution of neuritic plaque-related and independent tauopathies: implications for dementia staging

Abstract

Neuritic plaque (NP) formation can be dated in vivo. This analysis attempts to "date" the progression of neurofibrillary tangles (NFT) using the spatial distribution of NP as a reference. Autopsy data from 471 participants in the Honolulu-Asia Aging Study (HAAS) were combined into latent factor measures of NFT and NP counts. The variance in "early" and "late" NP pathology was used to estimate the spatial distribution of "early" and "late" NFT formation. A third latent factor representing "non-NP-related NFT" was also constructed. "Early" NP and "late" NP correlated significantly with objectively early and later cognitive performance, respectively. In contrast to our expectations, neocortical NFT correlated best with "early" NP pathology, while NFT in allocortical structures correlated best with "late" NP pathology. Therefore, the NP-related fraction of NFT appears to be co-localized spatially with NP. However, since the latter evolve corticofugally in time, this suggests that NP-related NFT do so as well. Corticotropic NFT formation must therefore be either unrelated to NP formation, a temporally distinct process, or both.

Keywords: Alzheimer's disease; dementia; mild cognitive impairment; neuropathology.

Figure 1

Observed NP-related NFT Counts are Most Strongly Associated with “Early” and “Late” NP lesions in the Same Regions of Interest*. * Restricted to subjects with unimpaired CASI > 70/100 at baseline. All observed indicators are adjusted for age at death, last CASI score, and education. χ² = chi-square; BCC = Browne Cudeck Criteria; CASI = Cognitive Abilities Screening Instrument; CFI = comparative fit index; df = degrees of freedom; NFT = neurofibrillary tangle (C = CA1 NFT, F = frontal lobe NFT, O = occipital lobe NFT, P = parietal lobe NFT, S = subiculum NFT, T = temporal lobe NFT); NP = neuritic plaque (Cnp = CA1 NP, Fnp = frontal lobe NP, Onp = occipital lobe NP, Pnp = parietal lobe NP, Snp = subiculum NP, Tnp = temporal lobe NP); RMSEA = root mean square error of approximation.