Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology

Autor: L. E. M. Wisse, R. de Flores, L. Xie, S. R. Das, C. T. McMillan, J. Q. Trojanowski, M. Grossman, E. B. Lee, D. Irwin, P. A. Yushkevich, D. A. Wolk, on behalf of the Alzheimer’s Disease NeuroImaging Initiative
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-11 (2021)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-021-00835-2
Popis: Abstract Background Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects. Methods Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156). Pathological diagnoses and semi-quantitative scores of MTL tau, neuritic plaques, α-synuclein, and TDP-43 pathology and MTL structural MRI measures from antemortem T1-weighted MRI scans were obtained. β-amyloid status (A+/A−) was determined by CERAD score and neurodegeneration status (N+/N−) by hippocampal volume. Results SNAP reflects a heterogeneous group of pathological diagnoses. In ADNI, SNAP (A−N+) had significantly more neuropathological diagnoses than A+N+. In the A− group, tau pathology was associated with hippocampal, entorhinal cortex, and Brodmann area 35 volume/thickness and TDP-43 pathology with hippocampal volume. Conclusion SNAP had a heterogeneous profile with more mixed pathologies than A+N+. Moreover, a role for TDP-43 and tau pathology in driving MTL neurodegeneration in the absence of β-amyloid was supported.
Databáze: Directory of Open Access Journals